Columbia  Wini\}tviitp 

in  tfje  Citp  of  ^eto  gorfe 

COLLEGE  OF  PHYSICIANS 
AND  SURGEONS 


Jf  rom  tJje  Hihtatp  of 

Br.  CJjn'jftian  13.  I^erter 

IDonateb  b|> 

iHrs;.  J^enrp  B.  ©akin 

1920 


COLUMBIA    UNIVERSITY 

EDWARD    G.    JANEWAY 

MEMORIAL    LIBRARY 


GOUT 


ITS    PATHOLOGY   AND    TREATMENT 


Founded  on  the  Goulstonian  Lectures  on  "  The  Chemistry  and 
Patholog-y  of  Gout,"  delivered  by  the  author  before  the  Royal 
College  of  Physicians  of  London  in  1897  ;  with  the  addition  of 
some  recent  investigations  concerning  the  Treatment  of  Gout, 
and  a  detailed  account  of  the  Treatment  of  the  various  forms 
of  Gout. 


BY 

ARTHUR  P.  LUFF 

M.D.IvOND.,    B.SC,    F.R.C.P. 

PHYSICIAN  IN  CHARGE  OF  OUT-PATIENTS,  AND  LECTURER  ON  FORENSIC 
MEDICINE    AT   ST.    MARY'S   HOSPITAL 


NEW  YORK 

WM.   WOOD  &  CO. 

MDCCCXCIX 


PREFACE. 


Part  I.  of  this  book  is  mainly  a  reproduction  of 
the  Goulstonian  Lectures  on  "  The  Chemistry  and 
Pathology  of  Gout,"  delivered  in  1897  before  the 
Royal  College  of  Physicians  of  London.  Part  IL 
deals  with  the  causation  of  gout,  its  various  forms 
and  its  diagnosis  and  prognosis.  Part  IIP  includes 
a  series  of  investic^ations  undertaken  with  the 
objects  of  ascertaining  the  various  conditions 
affecting  the  formation  and  removal  of  gouty 
deposits,  the  influence  of  alcoholic  drinks  on  the 
gouty  process,  the  solvent  effect  of  the  mineral 
constituents  of  various  vegetables  on  gouty  de- 
posits, and  the  value  of  certain  drugs  in  effecting 
the  removal  of  such  deposits.  Part  IV.  deals  with 
the  treatment  of  gout  and  of  gouty  conditions, 
especially  in  the  light  of  the  knowledge  gained  by 
recent  investigations.  The  subject  of  diet  has 
been  carefully  dealt  with,  and  a  classification  of  the 
various  mineral  waters  is  given  according  to  their 
therapeutic  value  in  the  treatment  of  the  various 

forms  of  gout. 

ARTHUR  P.  LUFF. 

31,  Weymouth  Street,  Cavendish  Square,  W. 
October,  1898. 


CONTENTS. 

PART     I. 

THE     PATHOLOGY    OF     GOUT, 

CHAPTER   I.  PAGE 

Uric  acid  and  its  compounds — Discussion  of  the  various  theories 
as  to  the  causation  of  gout — View  that  excess  of  some 
compound  or  compoiinds  of  uric  acid  constitutes  tlie 
primary  cause  of  gout — View  that  ulloxur  bases  con- 
stitute the  poison  of  gout — View  that  morbid  changes  in 
the  structure  of  tissues  constitute  the  primary  cause  of 
gout — View  that  nervous  disturbance  constitutes  the 
primary  cause  of  gout 1 

CHAPTER    II. 

Cause  of  the  presence  of  ui'ic  acid  in  the  blood  of  gout — Deficient 
excretion  of  uric  acid  in  gouty  subjects — Estimation  of 
uric  acid  in  the  urine — Detection  and  estimation  of  uric 
acid  in  blood 25 

CHAPTER    III. 

Seat  or  seats  of  formation  of  uric  acid — Uric  acid  not  a  normal 
constituent  of  the  blood — Pathological  conditions  under 
which  uric  acid  appears  in  the  blood 36 

CHAPTER    IV. 

The  renal  origin  of  gout — Association  of  kidney  affections  with 
gout — Association  of  renal  disease  with  the  presence  of 
uric  acid  in  the  blood — Nature  of  the  kidney  affection 
which  causes  gout 52 

CHAPTER    V. 

Origin  of  uric  acid — Formation  of  uric  acid  from  urea  in  the 
kidneys — Uric  acid  foraiation  and  liver  disease — Foi-ma- 
tion  of  uric  acid  from  nuclein — Different  modes  of 
formation  of  uric  acid  in  health  and  in  blood  disorders     .      64 


vi  Gout. 


CHAPTER    VI.  PAGE 

Composition  of  the  amorphous  urate  deposit  of  urine — Causes 
of  uratic  deposition — Formation  of  the  gouty  deposit — 
Time  occupied  in  the  conversion  of  sodium  quadriurate 
into  biurate — Seats  of  uratic  deposition  in  gout  .         .       83 

CHAPTER    TIL 

Causes  affecting  the  deposition  of  sodium  biurate— Reasons  for 
the  special  selection  of  the  great  toe  and  ear  as  seats  of 
gouty  deposits — Cause  of  the  inflammation  accompanying 
the  gouty  paroxysm 92 


PART     II. 

.ETIOLOGY  OF  GOUT— THE  VARIOUS  FORMS  OF  GOUT 
AXD  THEIR  CLINICAL  FEATURES  —  DIAGNOSIS 
AND    PROGNOSIS. 

CHAPTER    VIII. 

.Etiology  of  gout — Predisposing  causes  of  gout — Exciting  causes 
of  gout — Acute  gout — Chronic  gout — Saturnine  or  lead 
gout — Irregular  or  abarticular  gout   .        .         .        .         .105 

CHAPTER    IX. 

In-egular  gout  affecting  the  alimentary  tract — Irregular  gout 
affecting  the  air-passages  and  lungs — Irregular  gout 
affecting  the  heart  and  vessels — Iiregular  gout  affecting 
the  nervous  system — Irregular  gout  affecting  the  genito- 
urinary system — Irregular  gout  affecting  the  skin — Gouty 
glycosuria  and  diabetes  —  Gouty  hepatic  congestion — 
Gouty  affections  of  the  eye  and  ear — Retrocedent  or 
metastatic  gout — Diagnosis  and  prognosis  of  gout     .        .     IIG 


PART     III. 

THE      AUTHOR'S       INVESTIGATIONS      OF      CERTAIN 

POINTS     CONNECTED     WITH     THE     TREATMENT 

OF     GOUT. 

CHAPTER   X. 

Experimental  investigation  of  certain  conditions  and  factors 
affecting  the  solubility  and  the  precipitation  of  sodium 
quadriurate  and  sodium  biurate 128 


Contents.  vii 


CH.\PTER    XI.  PAGE 

Experimental  investigatiou  of  the  influence  exerted  by  the 
mineral  constituents  of  meat,  milk,  and  vegetables  re- 
spectively on  the  solubility  of  sodium  biurate — The  in- 
fluence of  alcoholic  beverages  on  the  gouty  process    .         .140 

CHAPTER    XIL 

Experimental  investigation  of  the  relative  effects  exerted  by 
the  mineral  constituents  of  various  vegetables  on  the 
solubility  of  sodium  biurate — Experimental  investigation 
of  the  influence  exerted  by  the  mineral  constituents  of 
various  vegetables  in  retarding  the  conversion  of  sodium 
quadriiu'ate  into  sodium  biurate — The  vegetables  most 
beneficial  to  gouty  subjects loO 

CHAPTER    XIII. 

Reasons  for  believing  the  treatment  of  gout  by  alkalies  to  be 
erroneous—  Expeiimental  investigation  of  the  value  of  the 
treatment  of  gout  by  the  various  alkalies,  by  piperazine 
and  by  lysidine — Reasons  for  believing  the  ti'eatment  of 
gout  by  salicylates  to  be  erroneous — Experimental  in- 
vestigation of  the  value  of  the  treatment  of  gout  by 
salicylates — General  conclusions         .         .         .         .         .176 


PART     IV. 

THE  TREATMENT  OF  GOUT  AND  OF  GOUTY 
CONDITIONS. 

CHAPTER  XIV. 

The  general  principles  on  which  the  treatment  of  gout  is  based 
— Examination  of  the  urine  —Treatment  of  acute  gout — 
Diet  in  acute  gout— The  action  of  colchicum — Treatment 
of  subacute  and  chronic  gout— Means  of  checking  the 
excessive  formation  of  ui'ic  acid — Means  of  promoting  the 
elimination  of  \mc  acid — Local  treatment  of  gouty  joints     199 

CHAPTER    XV. 

Treatment  of  retrocedent  or  metastatic  gout — Treatment  of  the 
various  forms  of  irregular  gout — Treatment  of  gouty 
glycosuria  and  diabetes — Preventive  treatment  of  gout — 
Diet  in  gout  —Alcohol  in  gout 213 


viii  Gout. 


CHAPTER    XVI.  PAGE 

The  uses  of  mineral  waters  iu  the  treatment  of  gout — The 
mineral  waters  best  suited  for  the  removal  of  gouty 
deposits — Classification  of  the  mineral  waters  used  in 
the  treatment  of  gout — The  simple  waters,  or  waters 
comparatively  free  from  sodium  salts — Simple  alkaline 
Avaters— Alkaline  sulphated  waters— Alkaline  muriated 
waters — Common  salt  or  muriated  waters — Sulphur 
waters— Hot  and  cold  mineral  watei-s — Classification  of 
mineral  waters  according  to  their  therapeutic  value  in  the 
treatment  of  the  various  forms  of  gout       ....     226 

Index 243 


fart  1. 


THE    PATHOLOGY    OF    GOUT. 


CflAPTER    I. 

Uric  acid  and  lis  cotiipounds — Discussion  0/ the  va7-ions 
theories  as  to  the  causation  of  gout — Yiev:)  that  ex- 
cess of  some  comjwund  or  compounds  of  itric  acid 
constitutes  the  primary  cause  of  gout — View  that 
aUoxur  bases  constitute  the  poisori  of  gout — Vieio 
that  morbid  changes  in  the  structure  of  tissues 
constitute  the  primary  cause  of  gou' — Vieio  that 
nervous  disturbance  constitutes  the  i^rimary  cause 
of  gout. 

Gout  is  the  manifestation  of  a  number  of  morbid 
tendencies,  some  of  which  n:iay  be  inherited  and 
some  acquired,  and  which  result  in  the  different 
diseases  associated  with  the  arthritic  diathesis. 
If  the  joints  are  aftected,  articular  or  regular  gout 
results :  if  other  oroans  or  tissues  are  affected,  then 
irregular  gout  is  produced. 

Gout  is  associated  with  the  presence  of  an 
excess  of  uric  acid  in  the  blood,  and  the  questions 
that  will  be  first  dealt  with  mainly  resolve  them- 
selves into  the  mode  or  modes  by  which  the  uric 
acid  is  produced  and  introduced  into  the  blood, 
the  source  or  sources  of  its  production,  the  relation- 
ship that   it   bears   to    the   gouty   paroxysm   and 


2  The  Pathology  of  Gout. 

to  the  other  manifestations  of  gout,  and  the 
factors  or  conditions  which  influence  its  formation 
and  its  injurious  action. 

URIC   ACID   AND   ITS   COMPOUNDS. 

Uric  acid  is  a  bibasic  acid,  the  formula  of  which 
is  H3(C5H2N403).  This  acid  forms  the  following 
three  classes  of  salts : — (1)  The  neutral  urates,  in 
which  a  metal  takes  the  place  of  all  the  displace- 
able  hydrogen,  such  as  Na2C-H2N403,  the  neutral 
sodium  urate.  (2)  The  biurates,  in  which  a  metal 
takes  the  place  of  half  the  displaceable  hydrogen, 
such  as  NaHCjHoN^Oo,  the  sodium  biurate.  The 
biurates,  although  acid  salts  in  constitution,  are  not 
acid  to  test  paper.  (3)  The  quadriurates,  in  which 
a  metal  takes  the  p]iiCfi-_QlLxaifizfbiixtliaiL^^ 

-  placeable  hydrogen  of  two  molecules  of.  uric  acid  ^ 
such  as  NaHC^HoN^Os,  HoC^HoN^Oa,  the  sodium 

^  qunrlriurate  Of  these  three  classes  of  salts  the 
neutral  urates  cannot  exist  in  the  living  organism, 
and  therefore  take  no  part  in  the  pathology  of 
gout.  It  is  also  important  to  understand  that 
uric  acid  does  not  and  cannot  exist  in  the  blood 
in  the  free  state  under  any  conditions  whatsoever. 

Tbfi  ^odimn  qnn|lrinra.tft  is  t.bn  solnblo.  nru?_np.iH^ 
p.(^m pound  which  is  originally  contained  in  th^ 
^  blood  of  gouty  subjects,  and  this  substance,  as  jusj 
mentioned^  is  a  derivative  of  two  molecules  of  uric 
acid  in  which  sodium  is  substituted  for  one-fourth 
of  the  displaceable  hydrogen,  or,  in  other  words, 
it  is  a  molecular  combination  of  sodium  biurate 
with    uric    acid.       This    sodium     quadriuratc    is. 


Formation  of  Sodium  Bi urate.  3 

however,  an  unstable  body,  and  after  a  certain  time 
it  unites  with  some  of  the  sodium  carbojiato  of  the 

, blood  to  form  sodium  biurate,  which,  if  produced 

in  larger  quantities  than  the  fluids  of  the  body  can 
retain  in  solution,  becomes  deposited  in  various 
structures  in  the  crystalline  form. 

This  conversion  of  sodium  quadriurate  into  the 
biurate  by  the  sodium  carbonate  of  the  blood  is 
shown  in  the  following  equation  : — 

2  /NaHCgHoN.Og,  H2C5H2N403\  +  NaoCOg  = 

^  Sodium  Quadi-iurate  ^  Sodium 

Carbouate 

4  NaHC^HoN^O.,  +  COo  +  H,0 

Sodium  Biurate  v 

The  sodium  quadriurate  is,  therefore,  to  be 
regarded  as  a  comparatively  soluble  but  very  un- 
stable compound,  whilst  the  sodium  biurate  is 
comparatively  insoluble  but  very  stable.  ^ 

Murexide  test  for  uric  acid. — If  two  or  three 
drops  of  strong  nitric  acid  are  added  to  a  fragment 
of  uric  acid  in  a  porcelain  dish,  and  heat  gently 
applied  until  all  the  nitric  acid  is  driven  off,  a 
reddish-coloured  residue  (alloxan)  will  be  left. 
If,  when  the  dish  is  cold,  a  few  drops  of  solution  of 
ammonia  are  added  to  this,  a  beautiful  crimson- 
purple  colour  is  developed,  due  to  the  production 
of  murexide  by  the  action  of  the  ammonia  on 
alloxan.  This  is  an  extremely  delicate  test,  and 
the  one-hundredth  part  of  a  milligramme  of  uric 
acid  may  be  detected  by  this  reaction. 

THEORIES  AS  TO  THE  CAUSATION  OF  GOUT. 

Of  the  various  theories  to  account  for  the 
production   of   gout    the    humoral    theories   have 


4  The  Pathology  of  Gout, 

been  to  the  front  for  many  centuries  at  various 
periods  in  the  history  of  the  disease.  Galen  was 
one  of  the  first  to  teach  that  tophi  arose  from 
the  desiccation  of  collected  and  pathologicall}^ 
altered  humours. 

Cullen,  who  was  the  great  opponent  of  the 
ancient  humoral  theory  of  gout  in  the  latter  half 
of  the  last  century,  admitted,  however,  that  in 
some  instances  a  peculiar  matter  appears  in  gouty 
patients,  but  he  considered  that  it  was  the  effect 
and  not  the  cause  of  the  malady.  Uric  acid  was 
discovered  in  the  urine  by  Scheele  in  1775,  and  in 
1787  Wollaston  demonstrated  its  presence  in  gouty 
concretions.  These  discoveries  did  not,  however, 
bring  to  light  the  important  part  played  by  uric 
acid  in  gout.  It  was  in  1847  that  Sir  Alfred 
Garrod  first  found  uric  acid  in  the  blood  of  gouty 
subjects  in  the  form  of  a  sodium  salt.  The  dis- 
covery of  uric  acid  in  the  blood  of  gouty  patients 
eventually  led  to  the  much-discussed  question 
as  to  whether  it  was  the  cause  or  the  result  of 
gout.  Those  who  hold  the  former  view  were  in 
their  turn  divided  as  to  whether  the  uric  acid 
compound  only  exerted  its  baneful  effects  when 
it  had  crystallised  out  of  the  blood  and  had  become 
deposited  in  the  affected  tissues,  or  whether,  while 
still  circulating  in  the  blood,  it  exercised  a  true 
toxic  influence.  The  various  views  held  as  to  the 
primary  cause  of  gout  may  be  classified  into  the 
three  following  groups : — (1)  Excess  of  uric  acid 
regarded  as  the  primary  cause  ;  (2)  morbid  changes 
in  the  structure  of  tissues  regarded  as  the  primar}- 


The  Causation  of  Gout.  5 

cause ;  and  (3)  nervous  disturbance  regarded  as  the 
primar}^  cause. 

The  following  is  a  brief  review  of  the  various 
opinions  held  as  to  the  primary  causation  of  gout, 
adopting  the  classification  just  given : — 

L — Excess    of    uric    acid    regarded    as    the 

PRIMARY   CAUSE   OF   GOUT. 

This  group  may  be  divided  into  two  sections 
accordingly  as  the  uric  acid  compound  is  regarded 
as  exerting  its  baneful  effect  in  the  crystalline  state 
or  in  the  dissolved  state. 

1,  The  uric  acid  compound  regarded  as  acting 
passively  and  physically  while  in  the  crystalline 
state. — Sir  Alfred  Garrod  and  Sir  William  Koberts 
are  the  two  principal  exponents  of  this  view,  which 
regards  gout — in  so  far  as  its  phenomena  depend 
on  uric  acid — as  a  disease  the  manifestations  of 
which  are  proximately  due  to  mechanical  injury. 
Sir  Alfred  Garrod  holds  that  every  paroxysm  of 
gout  is  attended  by  a  crystalline  deposit  of  sodium 
biurate,  and  that  this  deposit  exercises  chiefly 
a  mechanical  effect.  He  explains,  in  connection 
with  articular  gout,  that  when  the  blood,  for  some 
reason  or  other,  is  incapable  of  holding  the  uric 
acid  compound  in  solution,  it  is  deposited  in  an 
articular  cartilage  which  is  specially  predisposed 
for  its  reception.  Such  predisposition  is  generally 
caused  by  its  being  the  seat  of  former  injury  or 
disease.  The  crystallisation  of  the  biurate  within 
the  interstices  of  the  cartilage  then  provokes  the 
inflammatory  changes,  so  that  the  deposition  is  the 


6  The  Pathology  of  Gout, 

cause  of  the  inflamTiiation.  Sir  William  Roberts 
is  of  opinion  that  uric  acid  probably  does  not 
possess  any  inherent  poisonous  quaUty,  and  that  as 
long  as  it  remains  in  solution  it  produces  no 
harmful  results.  The  mischief  that  it  is  capable 
of  producing  only  results  from  its  precipitation 
or  crystallisation  as  sodium  biurate  in  the  tissues 
or  fluids  of  the  body.  He  considers  that  the 
inflammation,  pain,  swelling,  and  the  remoter 
secondary  degenerative  changes  of  regular  gout 
are  quite  explicable  by  regarding  the  crystalline 
biurate  which  is  precipitated  in  the  cartilaginous 
and  fibrous  structures  of  the  joints  as  exerting 
a  mechanical  action  as  a  foreign  body.  Cornil 
and  Ranvier  also  favour  the  idea  that  the  crystal- 
line uratic  deposit  in  cartilages  produces  inflamma- 
tor}^  changes  by  its  mechanical  irritation. 

POSSIBLE   CAUSE   OF   IRREGULAR   GOUT. 

Sir  William  Roberts  even  considers  that  the 
manifestations  of  irregular  gout  may  be  due,  like 
the  arthritic  manifestations,  to  uratic  deposition 
— that  is,  to  actual  precipitation  of  crystals  of 
sodium  biurate  into  the  connective  and  fibrous 
structures  of  the  implicated  organs,  whether  the 
liver,  heart,  lungs,  or  brain,  or  into  the  iibrous 
sheaths  of  the  nerves  controlling  the  functions  of 
the  affected  viscera.  He  is  further  of  opinion  that 
the  presence  in  the  blood  of  scattered  needles  of 
sodium  biurate  might  constitute  foci  around  which 
clotting  might  take  place,  and  that  the  thromboses 
not   unfrequently   observed  in  gouty  cases  might 


Causation  of  Irregular  Gout.  7 

thus  be  accounted  for.  The  various  locahties  in 
the  body,  apart  from  the  joints,  in  which  uratic 
deposits  have  been  found,  will  be  referred  to  later 
{see  p.  90),  but  as  regards  the  possible  de- 
position of  sodium  biurate  in  nervous  structures 
constituting  the  exciting  cause  of  some  of  the 
pains  and  affections  of  different  viscera  peculiar 
to  irregular  gout,  it  may  be  of  interest  to  mention 
here  the  following  facts : — C'rystals  of  sodium 
biurate  have  been  found  by  Watson,  Gairdner, 
and  Dafour  on  the  cerebral  meninges  ;  by  Schroeder 
van  der  Kolk  in  the  neurilemma  of  peripheral 
nerves  ;  and  by  Cornil  in  the  cerebro-spinal  fluid. 

With  regard  to  the  manifestations  of  irregular 
gout  being  due  to  uratic  deposits  in  the  affected 
viscera,  it  is  true  that  observations  on  the  subject 
are  very  limited  in  number.  But,  in  the  first 
place,  it  should  be  remembered  that  such  irregular 
uratic  deposits  are  extremely  likely  to  escape 
observation  in  the  post-mortem  room,  unless  very 
carefully  looked  for  by  the  aid  of  the  microscope ; 
and,  in  the  second  place,  it  is  highly  probable 
that  such  deposits  would  become  dissolved  during 
life  as  the  attack  of  irregular  gout  passes  off. 

AMORPHOUS   QUADRIURATES   NOT   IRRITANTS. 

The  question  might  be  raised  that  if  the  crystal- 
line biurate  always  acts  as  an  irritant,  why  should 
not  the  semi-solid  urinary  excrement  of  birds 
and  serpents  set  up  kidney  mischief  by  acting 
as  an  irritant  to  the  kidneys  during  its  excretion  ? 
The  reason  is  that  the  urinary  excrement  of  birds 


8  The  Pathology  of  Gout. 

and  serpents  is  composed  of  an  amorphous  quadri- 
iirate,  and  that  in  the  amorphous  condition  it 
is  incapable  of  acting  as  an  irritant.  Moreover, 
it  is  possible,  as  Sir  William  Roberts  has  suggested, 
that  the  uratic  excrement  passes  through  the 
tubules  of  the  kidneys  of  birds  and  reptiles  in 
the  gelatinous  form,  Avhich  could  not  produce 
the  mechanical  irritation  that  a  crystalline  deposit 
would  be  liable  to  cause. 

2.  The  uric  acid  compound  regarded  as  acting 
as   a  poison  or  irritant  while  in  the  dissolved 
state. — This   view,    while   holding    that   the    uric 
acid    compound   is   the   primary    cause   of    gout, 
regards  it   as   producing   morbid   changes   in  the 
structure   of  tissues  Avhile  remaining  in  the  dis- 
solved  state.     Many   writers   and   observers   have 
supported   the   view   that,   apart   from    the    local 
trouble   in    the  joints   caused    by    the    deposited 
sodium  biurate  acting  as  an  irritant,  the  soluble 
uric  acid   compound   which  is  circulating  in  the 
tiuids   of  the   body   acts   as   a   poison,    the   toxic 
effects    of   which   are   responsible   for    a    number 
of  the  symptoms  associated  with  the  gouty  state. 
Ffeitfer  holds   the   somewhat   peculiar   view   that 
a   compound   of  uric    acid   is   deposited   in   both 
healthy    and    diseased    portions    of    the    body — 
apparently     without      producing      any     marked 
symptoms — and    that  an  acute  attack  of  gout  is 
caused   b}-  the  blood  re-dissolving   this  deposited 
uric  acid  compound,  owing  to  a  temporary  increase 
in  the  alkalinity  of  the  blood,  and  that  dissolved 
in  the  blood  in  this  concentrated   form    the  uric 


Uric  Acid  not  a  Poison.  9 

acid  compound  acts  as  a  chemical  poison.  That 
this  view  is  untenable  is  evident  when  it  is 
remembered  that  uric  acid  is  deposited  as  the 
sodium  biurate,  and,  as  will  be  shown  later  {see 
pp.  137 — 139),  the  solubility  of  this  body  in  a  fluid 
medium  is  not  heightened  by  an  increased  alkalinity 
of  that  medium. 

URIC    ACID    NOT   A    POISOX. 

Sir  William  Roberts  ^  argues  that  the  accept- 
ance of  the  theory  that  uric  acid  possesses  a  toxic 
action  is  difficult  for  the  following  two  reasons : — 
(1)  That  there  is  no  direct  experimental  proof  that 
uric  acid  is  a  toxic  agent ;  and  (2)  that  although 
the  fluids  of  the  body  of  a  gouty  man,  on  the  eve 
of  an  outbreak  of  acute  gout,  are  impregnated  with 
sodium  biurate  to  saturation,  yet  such  a  person 
does  not  show  any  signs  of  poisoning,  but  enjoys 
complete  immunity  from  toxic  symptoms  until  the 
sudden  advent  of  the  arthritic  attack.  Another 
fact  which  is  strongly  opposed  to  the  view  that 
uric  acid  is  a  toxic  ao^ent  is  that  in  cases  ot" 
leucocythsemia  and  severe  auEemia  the  blood  is 
frequently  highly  charged  with  uric  acid  in  the 
form  of  sodium  quadriurate  without  the  production 
of  any  toxic  symptoms  that  could  be  referred  to 
the  uric  acid  compound. 

ALLOXUR    BASES    REGARDED    AS   THE    POISOX   OF 

GOUT. 

Kolischf  considers  that  some   antecedents   or 
allies   of  uric   acid   are   responsible  for  the    toxic 

*  Croonian  L3ctures  :   "  Uric  Acid  Gravel  and  Gout,"   1892. 
t  Wiener  klinische  JFochenschrift,  1895,  p.  787. 


lo  The  Pathology  of  Gout. 

effect  Avhich  he  believes  constitutes  the  priinarj^ 
cause  of  gout.  His  view  is  that  the  graver  mani- 
festations of  gout  only  make  their  appearance 
when  the  functions  of  the  kidneys  become  im- 
paired from  any  cause,  and  since  he  finds  that 
in  the  urine  of  the  gouty  there  is  an  increase 
of  alloxuric  substances,  and  also  that  alloxur  bases 
cause  changes  in  the  kidneys  resembling  parenchy- 
matous degeneration,  he  infers  that  these  bases^ 
are  concerned    in   the   production   of  the   kidney 


affiRntifjp  which  prpped^^  thft  develo_pment  of 
His  theory  is  that  during  normal  action  of  the 
kidneys  the  greater  part  of  the  alloxur  bases  is 
excreted  as  uric  acid ;  but  when  the  structures 
which  form  uric  acid  are  enfeebled  there  is  an 
increased  excretion  of  alloxur  bases,  with  con- 
comitant toxic  effects.  Kolisch's  views  have  re- 
ceived some  confirmation  by  Weintrand,  "^  who  has 
also  found  an  excessive  excretion  of  alloxuric 
substances  in  the  urine  of  gouty  patients.  On  the 
other  hand,  they  are  controverted  h^^  the  observa- 
tions of  Schmoll,t  His,|  Laquer,§  and  Mafatti,|| 
who  failed  to  find  any  increased  excretion  of 
alloxuric  substances  in  the  urines  of  gouty  patients. 

II. — Morbid    changes    in    the    structure    of 

TISSUES     REGARDED     AS     THE     PRIAIARY    CAUSE 
OF   GOUT. 

This  group  may  be  divided  into  two   sections 

♦  Charite  Annalen,  1895,  xx.,  p.  215. 

t  Zeitsehrifc  fur  klinische  Medicin,  1896,  xxix.,  p.  510. 

J  Jierliner  /clinische  IFochenschrift,  1896,  xxxiii.,  p.  70. 

^  Verhandlungen  des  Cong.  f.  innere  Med.,  1896,  xiv.,  p.  33. 

II  Wiener  klinische  Wochenschrift,  1896,  ix.,  p.  723. 


EnsTF./N's   Views.  ii 

accordingly  as  the  morbid  changes  are  produced 
by  the  presence  of  a  sokible  urate  or  not. 

1.  Necrotic  changes  in  the  affected  tissues 
regarded  as.  the  primary  cause  of  gout,  the 
necrosis  being  due  to  the  presence  of  dissolved 
urates. — Ebstein,^  who  has  devoted  a  considerable 
amount  of  time  to  the  experimental  study  of 
the  causation  of  gout,  is  the  great  exponent  of 
this  view.  His  theory  is  that  a  destructive  or, 
as  he  terms  it,  a  necrotising  process  is  produced 
in  the  cartilages  or  other  implicated  tissues  by 
uric  acid  in  one  form  of  combination,  and  that, 
following  this,  the  uric  acid  in  another  form  of 
combination  is  deposited  in  the  necrosed  areas. 
In  other  words,  that  a  destructive  process  always 
precedes  the  process  of  deposition,  both  processes 
being  due  to  uric  acid,  but  in  different  states  of 
combination.  Ebstein  maintains  that  uratic 
crystals  only  form  in  necrotic  tissues,  never  in 
healthy  tissues.  He  regards  the  necrosis  of  tissue 
and  the  subsequent  uratic  deposits  as  together 
constituting  the  characteristic  ensemble  of  the 
gouty  process.  His  theory  assumes  that  the 
irritant  is  the  neutral  sodium  urate  in  the  dissolved 
state,  and  that  the  first  step  in  the  gouty  process 
consists  in  a  stasis  of  the  lymph  stream,  followed 
by  the  infiltration  of  the  tissue  in  circumscribed 
areas  by  the  lymph  containing  the  dissolved 
neutral  urate.  The  neutral  urate,  according  to 
his  view,  acts  as  a  chemical  irritant,  and  sets 
up  a  necrotising  process  in  the  implicated  tissues, 

*  "  Die  Natur  und  Behandlung  der  Gicht,"  1882. 


12  The  Pathology  of  Gout. 

and  finally  produces  complete  necrosis  of  the 
tissues  in  the  affected  areas.  The  necrotising  and 
necrotic  portions  of  the  tissues  provoke  irritation 
of  the  surrounding  parts,  and  so  produce  the  in- 
flammatory phenomena  of  gout.  Ebstein  assumes 
that  the  process  of  necrosis  generates  a  free  acid, 
which  converts  the  neutral  urate  present  in  the 
fluids  of  the  body  into  the  acid  urate,  which  sub- 
stance is  then  deposited  in  the  crystalline  form 
in  the  fully  necrosed  areas.  No  mention  is  made 
of  the  nature  or  name  of  this  hypothetical 
acid. 

ebstein's    experiments. 

To  support  this  theory  Ebstein  relies  upon 
two  different  classes  of  experiments  conducted  by 
him.  One  class  consists  of  his  examination  of  the 
organs  and  tissues  of  birds  that  he  considered  he 
had  rendered  gouty,  by  preventing  the  elimination 
of  their  urinary  secretion.  The  other  class  of 
experiment  consists  of  observations  on  the  irritant 
effect  of  a  solution  of  a  sodium  urate  on  the 
delicate  corneal  tissue  of  the  eye.  As  I  venture  to 
differ  from  the  deductions  that  Ebstein  has  drawn 
from  his  experiments  and  observations,  I  propose 
to  describe  his  methods  of  experimentation,  and 
briefly  to  criticise  his  deductions  therefrom. 

ebstein's  experiments  on  birds. 

Ebstein's  first  series  of  experiments  consisted  in 
an  endeavour  to  induce  in  cocks  a  condition  which, 
from  the  anatomical  point  of  view,  he  considered 
was  analogous  to  the  gouty  state  in  man.     This 


Ebstein's  Experiments.  13 

he  effected  by  preventing  the  ehmination  of  their 
urinar}^  uratic  secretion  in  two  ways — (a)  by  liga- 
turing the  two  ureters,  and  so  damming  back  upon 
the  circulation  the  urates  which  would  otherwise 
have  passed  away;  and  (jj)  by  administering  to 
the  cocks  small  and  repeated  subcutaneous  in- 
jections of  the  neutral  potassium  chromate,  which 
Ebstein  considers  inhibits  the  passage  of  uric  acid 
through  the  kidneys  by  its  action  on  the  renal 
parenchyma,  and  so  causes  a  damming  back  upon 
the  circulation  of  a  portion  of  the  urates,  which 
normally  are  excreted  in  their  entirety  by  the 
kidneys.  In  the  bodies  of  the  birds  experimented 
on  uratic  deposits  were  found  in  the  articulations, 
in  the  tendon-sheaths,  in  the  liver,  and  in  the 
muscular  tissues.  Ebstein  found  that  the  deposi- 
tion of  urates  was  much  more  copious  and  more 
widely  spread  in  the  cocks  experimented  on  by 
injection  of  potassium  chromate  than  in  thoFe 
whose  ureters  were  ligatured.  This  difference  he 
referred  to  the  fact  that  he  could  keep  the  birds 
alive  for  a  long  time  while  subjecting  them  to 
the  action  of  potassium  chromate,  whereas  after 
ligaturing  both  ureters  they,  as  a  rule,  only  lived 
for  about  twenty-four  hours.  As  the  result  of 
these  experiments  Ebstein  came  to  the  following 
conclusions: — (1)  That  necrosing  and  necrotic 
processes  are  developed  in  various  organs  as  the 
result  of  some  irritant ;  (2)  that  uratic  deposits 
form  in  the  necrotic  areas  which  in  appearance 
resemble  the  gouty  deposits  of  man ;  (3)  that 
a  reactive  inflammation,  with  infiltration  of  small 


14  The  Pathology  of  Gout. 

cells,   is   set   up   in   the   neighbourhood   of    these 
necrotic  areas. 

CRITICISM     OF    EBSTEIN's    EXPERIMENTS    ON   BIRDS. 

This  class  of  experiments  therefore  consisted  of 
observations  of  the  uratic  deposits  formed  in  fowls 
when  the  elimination  of  their  uric  acid  is  prevented 
either  by  ligaturing  the  ureters,  or  by  the  pro- 
gressive disablement  of  the  kidneys  by  repeated 
subcutaneous  injections  of  potassium  chromate.  1 
do  not  think  that  the  morbid  processes  occurring 
under  these  conditions  in  fowls  can  be  considered 
as,  in  any  sense,  comparable  with  those  occurring 
in  connection  Avith  gout  in  man.  Ebstein  found 
uratic  deposits  in  th^  IIvpt  ar^d  nui^cular  tissues  oi' 
the  birds  experimented  on.  localities  where  they 
are  not  found,  at  all  events  to  any  appreciable 
extent,  in  human  gout.  From  this  one  may  fairly 
conclude  that  the  two  processes  cannot  be  con- 
sidered as  comparable.  Moreover,  since  the  fowl 
produces  and  eliminates  by  the  kidneys  so  large  a 
quantity  of  lu'ates,  the  more  or  less  sudden  stoppage 
of  kidney  excretion  must  necessarily  result  in  the 
damming  back  of  it  and  the  rapid  accumulation 
of  it  in  the  blood  and  tissues,  where,  as  Sir  William 
Roberts*  suggests,  it  would  probably  first  collect  in 
a  state  of  sohition  as  the  quadriurate,  which  would 
then  bo  precipitated  in  the  tissues  as  the  gelatinous 
biurate,  and  this  in  its  turn  would  be  changed  into 
the  crystalline  biurate. 

*  Cioonian    Lectures:    "  Uiic  Acid  Gravel  and   Gout,"   1892, 
p.  118. 


Ebstein's  Experiments.  i5 

ebstein's  experiments  with  urates. 

It  is  on  the  second  class  of  experiments  that 
Ebstein  depends  for  proof  of  his  assumption  that 
the  neutral  sodium  urate  is  capable  of  acting  as 
a  chemical  irritant  to  the  tissues,  and  of  pro- 
ducing in  them  the  necrotising  changes  which 
subsequently  lead  to  complete  necrosis  of  the 
affected  areas  of  the  implicated  tissues.  In  order 
to  show  that  a  combination  of  uric  acid  with 
sodium  acted  as  an  irritant,  Ebstein  took  a 
saturated  solution,  prepared  at  100^  F.,  of  uric 
acid  in  a  5  per  cent,  solution  of  sodium 
phosphate,  and  injected  it  into  the  peritoneal 
cavity,  into  the  kidney,  into  the  anterior  chamber 
of  the  eye,  into  the  cartilage  of  the  ear,  and  into 
the  cornea  of  a  rabbit.  Powdered  uric  acid  was 
also  introduced  by  insufflation  into  the  conjunctival 
fold  of  one  eye.  Yery  appreciable  changes  were 
produced  in  the  cornea  only,  and  it  was  in  this 
structure  that  Ebstein  studied  what  he  considers 
were  the  irritant  or  toxic  effects  of  uric  acid.  He 
found  that  these  injections  produced  a  modified  form 
of  inflammation  in  the  tissues  of  the  cornea.  As  a 
control  experiment  he  injected  into  the  cornea  of 
the  other  eye  a  simple  solution  of  sodium  phos- 
phate, or  water  containing  calcined-  magnesia  in 
suspension,  neither  of  which  produced  any  inflam- 
matory changes.  He  therefore  inferred  that  the 
inflammatory  changes  were  set  up  in  the  cornea 
by  the  urate  in  solution  acting  as  a  chemical 
irritant. 


1 6  The  Pathology  of  Gout. 

CRITICISM   OF   EBSTEIN's   EXPERIMENTS   WITH 
URATES. 

The  objection  to  this  method  of  experimenta- 
tion is  that,  in  the  tirst  place,  the  sohition  of  uric 
acid  in  sodium  phosphate  does  not  contain  the 
neutral  sodium  urate,  which  is  the  body  on  which 
Ebstein  relies  lor  the  production  of  the  initial 
irritant  effects  leading  on  to  the  necrotising  process. 
The  solution  would  contain  the  sodium  quadriurate 
or  the  biurate,  or  a  mixture  of  the  two.  Moreover, 
as  Sir  William  Roberts  has  pointed  out,  such  a 
saturated  solution  would  soon  begin  to  deposit  its 
urate  in  the  form  of  the  gelatinous  biurate,  which, 
infiltrating  the  affected  area  of  the  corneal  tissue, 
would  act  as  a  mechanical  irritant.  It  is,  there- 
fore, clear  that  all  the  corneal  changes  observed  by 
Ebstein  can  be  accounted  for  by  the  assumption  that 
they  are  caused  by  a  mechanical  irritant.  The  ex- 
periments of  Neubauer  are  opposed  to  the  view  that 
a  soluble  urate  circulating  in  the  blood  can  act  as 
a  poison  or  irritant  and  start  necrosis.  He  found 
that  the  administration  of  large  quantities  of  uric 
acid  to  rabbits  (as  much  as  twelve  grammes  in 
some  cases)  did  not  seem  to  cause  any  incon- 
\  venience.  Moreover,  is  it  likely  that  solutions  of 
urates  should  act  as  irritants,  when  their  passage 
through  the  kidneys  is  part  of  the  natural  elimina- 
tion of  nitrogen  in  man  ?  If  solutions  of  the  urates 
are  to  be  regarded  as  irritants,  then  the  kidneys 
would  never  escape  damage.  Another  important 
argument  which  militates  against  the  acceptance 


Criticism  of  Ebstein's  Experiments.       17 

of  Ebstein's  theory  is  that,  not  only  is  there  no 
proof  that  fh^  x\(^\^iv9^  Rnf|ii]Tn  nrate.  upon  whjiJi 
he  depends  foe- the  Dtfti'ting~-Qf-thje--gQuty  changes^!^ 
ever  exists  in  the  human  body,  but,  on  the  other 
hand,  there  is  strong  evidence  to  show  that  it 
never  can  exist  in  the  human  body.  The  neutral 
sodium  urate  is  an  extremely  caustic  and  unstable 
X I  compound,  and  is  decomposed  in  the  presence  of 
carbonates,  so  that  it  is  impossible  for  it  to  exist  in 
I  the  blood.  The  first  factor  upon  which  Ebstein 
relies  for  his  theory  of  the  causation  of  gout  there- 
fore disappears.  Moreover,  the  responsibility  for 
the  assumed  necrotic  changes  cannot  be  transferred 
from  the  neutral  sodium  urate  to  the  biurate, 
since  Pfeiffer  has  shown,  by  means  of  subcutaneous 
injections  of  a  solution  of  a  biurate,  that  although 
it  can  produce  pain  and  irritation,  yet  it  cannot 
cause  necrosis,  especially  when  in  so  weak  a  solu- 
tion as  must  occur  in  the  human  body.  The 
assumption  by  Ebstein  that  the  process  of  necrosis 
generates  an  acid  which  is  supposed  by  him  to 
convert  the  neutral  urate  into  the  acid  urate  is 
based  on  an  imperfect  acquaintance  with  the 
chemistry  of  the  urates.  Sir  William  Roberts  has 
shown  that  uric  acid  is  primarily  taken  up  by  the 
blood  and  lymph  as  a  quadriurate — not  as  a  neutral 
urate — and  he  has  also  proved  that  the  formation 
and  deposition  of  the  crystalline  biurate  are 
not  favoured  by  the  intervention  of  an  acid. 
Moreover,  in  connection  with  leucocytheemia  severe 
antemia,  and  other  diseases,  to  which  reference 
will  be  made  later,  we  know  that  a  considerable 
c 


iS  The  Pathology  of  Gout. 

qiia-ntit^of  uric  acid  may  be  present  in  the  blood 
in  the  form  of  sodium  quadriurate  without  giving 
)  rise  to  necrosis  of  tissues  anywhere. 

ebstein's  views  as  to  necrotic  changes  in 

GOUT. 

Ebstein  considers  that,  by  dissolving  out  the 
crystalhne  urates  from  tissues  in  which  they  are 
deposited,  he  is  able  to  demonstrate  the  existence 
of  necrosis  in  the  sites  previously  occupied  by  the 
uratic  deposit,  and  insists  that  the  crystalline 
urates  are  only  deposited  in  tissues  that  have 
undergone  necrotising  and  necrotic  changes.  This, 
however,  is  opposed  to  the  experience  of  such 
competent  observers  as  Sir  Alfred  Garrod,  Sir 
William  Roberts,  Sir  Dyce  Duckworth,  and  Cornil 
and  Ranvier.  I  have  also  frequently  examined 
sections  of  cartilages  containing  uratic  deposits 
which  have  not  shown  any  ncciosis  at  the  sites  of 
the  deposits,  and  in  which  the  cartilage  appeared 
to  be  practically  uninjured.  The  changes  that  may 
be  seen  in  cartilages  containing  a  dense  deposit 
of  sodium  biurate  are  quite  intelligible  on  the 
assumption  that  they  are  caused  in  part  by  the 
mechanical  pressure  of  the  crystals,  and  in  part  by 
the  intlanunation  and  subsequent  degeneration  set 
up  by  the  presence  of  the  crystalline  deposit.  If 
the  sodium  biurate  is  only  formed  and  deposited  in 
necrosed  areas,  how  is  it  that  crystals  of  sodium 
biurate  are  occasionally  found  free  in  the  synovial 
fluid  of  a  gouty  joint  ?     As  Sir  William  Roberts* 

*  Croonian  Lectures:    ''Uric  Acid   Gravel  and  (Jout,"    1892, 
p.  117. 


The  Causation  of  Gout.  19 

remarks  :  "  it  will  scarcely  be  contended  that  necro- 
tising  and  necrotic  processes  can  take  place  in 
synovia!" 

Sir  Dyce  Duckworth^  in  a  modified  sense 
believes  that  a  soluble  urate  may  act  as  an  irritant. 
Although  he  considers  that  gout  is  primarily  due 
to  a  disorder  of  the  nervous  system,  he  entertains 
the  additional  view  that  the  urate  in  solution  may 
set  up  degeneration  and  necrotic  changes  in  tissues. 
This  view  is  expressed  as  follows  :  "  It  can  hardly 
be  doubted  that  lesions  result  from  the  action  of 
uric  acid  in  solution  in  the  tissues,  and  that  thus 
both  acute  and  chronic  inflammatory  changes  may 
be  set  up  without  the  direct  influence  of  uratic 
deposit  as  an  alleged  irritant  in  joints  and  in  certain 
viscera,  notably  in  the  kidneys.  Degenerative 
changes  and  necrosis  also  appear  to  be  thus 
induced." 

2.  Inflammatory  or  degenerative  changes  in 
the  affected  tissues  regarded  as  the  primary 
cause  of  gout,  such  initial  changes  not  being 
caused  by  urates. — Dr.  Ord  in  1872  considered 
that  gout  was  due  to  a  special  iorm  of  degeneration 
in  some  of  the  fibroid  tissues,  resulting  in  an 
[.excessive  Formation  of  sodium  urate,  which  is  then 
discharged  into  the  blood,  and  is  subsequently 
deposited  in  those  parts  least  freely  supplied  with 
vascular  and  lymphatic  structures.  Dr.  Ord,  whose 
views,  in  this  particular,  have  been  supported  by 
Dr.  Norman  Moore  and  Mr.  Bowlby,  also  considers 
that  uratic  deposits  only   occur  in  tissues  which 

*  -'A  Treatise  on  Gout,"  1889,  p.  53. 


20  The  Pathology  of  Govt. 

have  previously  begun  to  degenerate.  Dr.  Berkart  ^ 
considers  that  the  severity  of  the  local  symptoms 
attending  an  attack  of  acute  gout  are  inconsistent 
with  the  assumption  that  they  are  produced  by  a 
primary  chondritis,  due  to  irritation  set  up  by  the 
deposition  of  sodium  biurate  in  the  articular  carti- 
lages. He  considers  that  the  vole  of  the  uric  acid 
is  one  of  a  humbler  kind  than  that  which  has 
hitherto  been  attributed  to  it.  In  his  opinion  the 
uratic  deposits  are  most  frequently  connected  with 
a  form  of  panarthritis,  or  a  general  inflammatory 
affection  c)f  the  joints,  which  chiefly  affects  the 
smaller  joints  of  the  extremities.  Without  assum- 
ing any  identity  between  arthritis  deformans  and 
gout,  he  considers  that  in  both  instances  the  disease 
probably  originates  in  some  kind  of  atrophy  of  the 
substance  of  the  bone,  that  the  degenerative  process 
then  attacks  the  cartilasfes  and  fibrous  tissues  of 
the  joints,  and  that  following  on  this  there  occurs  a 
necrosis  of  the  tissues  close  to  or  within  the  joint. 
This  necrosis,  he  considers,  is  the  primary  cause 
of  the  pain,  hypericmia,  collateral  oedema,  and  de- 
squamation of  the  skin  of  the  afl[ec ted  joint.  The 
degeneration  and  necrosis  ot  the  tissues  are  the 
result  of  a  profound  disturbance  of  nutrition. 
Dr.  Berkart  attributes  the  presence  of  the  urates  in 
the  blood  in  part  to  leucocytosis,  and  in  part  to  the 
formation  of  uric  acid  from  the  disintegration  of  the 
tissues ;  so  that  he  regards  the  uratic  deposits  as 
an  epiphenomenon.  and  not  as  the  cause  of  the 
gouty  paroxysm. 

*  Bid.  Mtd.  Joiirn.,  1895,  vol.  i.,  p.  243. 


The  Causation  of  Gout.  21 

III. — Nervous   disturbance   regarded   as   the 

PRIMARY   CAUSE    OF   GOUT. 

The  view  that  gout  is  intimately  connected 
with  disturbances  of  the  nervous  system  has  many 
supporters.  CuUen,  the  great  opponent  of  the 
humoral  theory  in  the  latter  half  of  the  last 
century,  considered  that  gout  mainly  depended  on 
an  affection  of  the  nervous  centres.  Sir  Dyce 
Duckworth,^  while  accepting  the  view,  as  previously 
mentioned,  that  uric  acid  has  some  connection 
with  gout,  considers  that  gout  is  primarily  depen- 
dent on  a  functional  disorder  of  a  definite  tract  of 
the  nervous  system,  and  that  the  part  specially 
involved  is  possibly  situated  in  the  medulla 
oblongata,  where  it  may  be  that  there  is  a  trophic 
centre  for  the  joints.  One  reason  that  Sir  Dyce 
Duckworth  gives  for  considering  this  possible  is 
the  relationship  of  gout  to  diabetes,  the  consider- 
ation of  which  has  led  him  to  the  belief  that  the 
portions  of  the  nervous  system  involved  in  the  tAvo 
diseases  cannot  be  far  apart  from  one  another. 
In  consequence  of  this  disorder  of  the  neurotrophic 
system  defects  of  nutrition  arise  which  not  only 
cause  undue  formation  of  uric  acid,  but  also 
inhibit  the  normal  destruction  of  that  body  in 
the  tissues  ;  at  the  same  time  the  renal  excre- 
tory power  for  uric  acid  appears  to  be  tempo- 
rarily inhibited  as  part  of  the  process  of  the 
gouty  paroxysm. 

Sir  Dyce  Duckworth,  therefore,  regards  gout  as 

*  "  A  Treatise  on  Gout,"  1889. 


22  The  Pathology  of  Gout. 

belonging  to  the  class  of  neuro-humoral  diseases, 
but  he  does  not  at  present  insist  on  the  localisation 
of"  the  primary  disturbance  in  a  limited  portion  of 
the  cerebro-spinal  axis.  He  draws  the  following  dis- 
tinction between  inherited  and  acquired  gout.  In 
primary  or  inherited  gout  the  toxaemia  is  depen- 
dent on  the  inherited  gouty  neurosis.  In  second- 
ary or  acquired  gout  the  toxaemia  arises  from 
the  digestive  and  excretorj^  organs  becoming  over- 
loaded, and  then,  if  with  this  toxaemia  there  is 
depression  and  exhaustion  of  the  nervous  system, 
the  gouty  neurosis  may  be  established  by  the 
morbid  blood  condition  aftecting  the  nutrition  of 
the  nervous  system.  Sir  Dyce  Duckworth  claims 
that  the  suddenness  with  which  an  acute  attack  of 
gout  comes  on,  preceded  as  it  is  usually  b}^  a  sense 
of  well-being  in  the  patient,  is  indicative  of  the 
nervous  origin  of  the  outbreak,  and  that  it  is  to 
the  instability  and  undue  sensitiveness  of  the 
nervous  system  in  the  gouty  that  the  manifesta- 
tions of  the  paroxysm  are  due. 

Dr.  Edward  Liveing^  considers  that  there  is 
much  to  be  said  in  support  of  the  view  that  gout 
is  the  manifestation  of  a  disorder  which  has  its 
primary  seat  in  the  nervous  system.  He  remarks 
that  the  view  that  uric  acid  exerts  a  toxic  influence 
upon  the  nervous  centres,  and  that  the  particular 
character  of  the  disorder  is  determined  by  the 
territory  involved,  is  one  that  presents  real  obstacles, 
on  account  of  the  limited  operation  attributed  to  a 
cause  so  general  in  its  nature. 

*  *'  Oa  Megrim  and  Sick  Headache,"  1873,  pp.  404-5. 


Nervous  System  and  Gout.  23 

l)r.  P.  W.  Latham^  regards  some  change  in  the 
nervous  system  as  the  most  important  factor  in  the 
etiology  of  gout.  He  thinks  that  such  change  is 
localised  in  the  medulla  oblongata,  or  in  the  spinal 
cord,  or  in  both,  and  that  this  nervous  disorder 
may  be  either  hereditary  or  acquired.  He  argues 
that  if  a  portion  of  the  medulla  oblongata  involving 
some  of  the  roots  of  the  vagus  be  the  part  affected, 
the  metabolism  of  the  liver  may  be  interfered  with, 
and  so  lead  to  the  formation  of  uric  acid.  He  also 
considers  that  if,  from  any  cause,  uric  acid  is  cir- 
culating in  the  blood,  it  would  act  as  a  poison  upon 
any  weak  spot  in  the  nervous  system,  and  that  it  is 
intelligible  that  it  might  act  upon  portions  of  the 
spinal  cord  which  control  the  nutrition  of  the 
joints,  and  so  cause  nutritive  changes  or  inflam- 
mation in  the  joints  connected  with  that  portion 
of  the  cord.  In  consequence  of  the  inflammation 
or  nutritive  changes  in  the  joints,  sodium  biurate 
becomes  deposited  in  them,  or  in  the  tissues  around 
the  affected  joint.  Dr.  Latham  explains  the  phe- 
nomena of  a  gouty  paroxysm  by  direct  stimulation 
of  sensory  nerves  by  uric  acid.  He  considers  that 
the  gout  associated  with  chronic  lead  poisoning 
may  be  explained  by  the  lead  acting  in  such  cases 
more  particularly  on  those  portions  of  the  spinal 
cord  which  are  concerned  in  gout. 

Dr.  Kalfe  held  the  view  that  the  accumulation 
of  uric  acid  in  the  blood  in  gout  was  due  to  non- 
conversion  into  urea  of  the  uric  acid  normally 
formed  in  the  tissues,  and  he  considered  that  the 

*  "  Croonian  Lectures/'  1886. 


24  The  Pathology  of  Gout. 

conditions  which  prevent  the  normal  destruction 
of  uric  acid  in  the  tissues  depend  probably  on 
disturbance  of  innervation. 

THE   author's    view   AS    TO    THE    PRIMARY    CAUSE 

OF     GOUT. 

From  a  careful  consideration  of  these  various 
views  as  to  the  primary  cause  of  gout,  I  am 
of  opinion  that  the  greatest  mass  of  evidence  is 
in  favour  of  the  view  that  a  salt  of  uric  acid 
is  the  materies  Tnorhi.  The  details  of  various 
experiments  that  support  this  view  will  be  given 
later. 


25 


CHAPTER    11. 

Cause  of  the  presence  of  uric  acid  in  the  hlooi  of  gout  — 
Deficient  excretion  of  uric  acid  in  gouty  subjects — - 
Estimation  of  uric  acid  in  urine — Detection  and 
estimation  of  uric  acid  in  hlood. 

CAUSE    OF    THE     PRESENCE     OF    URIC    ACID    IX    THE 
BLOOD   OF   GOUT. 

The  next  question  to  consider  is  whether  the 
excess  of  uric  acid  present  as  qnadriurate  and 
biurate  in  the  blood  in  gout  is  the  result  of  de- 
ficient excretion,  of  over-production,  or  of  deficient 
destruction.  All  observers  are  agreed  that  an 
abnormal  quantity  of  uric  acid  in  the  form  of  one 
or  other  of  its  salts  is  found  in  the  blood  in  gout. 
This  overcharofinof  of  the  blood  with  uric  acid  must 
be  due  to  one  or  more  of  the  following  causes : — 
(1)  Normal  production  and  deficient  excretion  of 
uric  acid;  (2)  over-production  and  normal  excre- 
tion of  uric  acid :  and  (3)  diminished  destruction 
of  uric  acid  by  imperfect  oxidation,  or  by  some 
other  means. 

This  last  theory  may  be  dismissed  at  once. 
There  is  no  proof  that  the  process  of  oxidation 
destroys  uric  acid ;  on  the  contrary,  there  is  proof 
that  uric  acid  is  produced  by  a  process  of  oxidation. 
Moreover,  not  only  is  there  no  proof  that  uric 
acid  is  produced  during  health  in  the  organs  and 
tissues  of  the  body  generally,  and  that  it  subse- 
quently undergoes  more  or  less  destruction,   but 


26  The  Pathology  of  Gout. 

there  are  good  reasons  for  believing  that  uric 
acid  is,  in  health,  only  formed  in  the  kidneys, 
and  never  appears  in  the  general  circulation  except 
under  pathological  conditions. 

With  regard  to  the  second  theory  of  over- 
production and  normal  excretion  of  uric  acid, 
there  is  abundant  experimental  proof  to  show 
that  an  increased  production  of  uric  acid  does 
not  lead  to  gout,  so  long  as  the  kidneys  remain 
in  a  normal  condition.  For  instance,  in  connection 
with  diseases  such  as  leucocythaemia  and  severe 
anaemia  there  is  an  over-production  of  uric  acid, 
but  no  development  of  gout.  In  these  diseases 
the  excessive  quantity  of  uric  acid  produced  is 
readily  excreted  by  the  kidnej^s,  as  is  shown  by 
the  large  amount  of  uric  acid  that  may  be  found 
in  the  urine.  In  addition,  gout  is  essentially 
a  disease  of  middle  age,  and  is  only  ver}^  excep- 
tionally met  with  in  childhood  and  in  youth, 
although  the  formation  of  uric  acid  is  greatest 
in  early  life,  and  apparently  diminishes  Avith  the 
advance  of  age. 

VIEW   THAT    DEFICIENT    EXCRETION    01'   URIC   ACID 
IS   CONNECTED   VriTH   GOUT. 

There  are  many  facts  to  support  the  view  that 
cfout  is  due  to  deficient  elimination  of  the  uric  acid 
normally  produced,  and  to  subsequent  absorption  of 
this  uric  acid  from  the  kidneys  in  consequence  of 
that  deficient  excretion.  That  there  is  a  deficient 
excretion  of  uric  acid  in  gout  is,  I  think,  justified  by 
the  following  facts.     Judging  as  far  as  is  possible 


Uric  Acid  Excretion. 


27 


by  averages,  recent  accurate  estimations  of  the 
excretion  of  uric  acid  show  that  in  gouty  subjects 
there  is  a  decrease  in  its  daily  excretion  as  com- 
pared with  healthy  individuals.  Pfeiffer  "^  compares 
the  quantities  of  uric  acid  contained  in  the  urine 
of  gouty  patients  at  various  ages,  in  whom 
the  complaint  had  not  yet  become  chronic,  with 
the  quantities  contained  in  the  urines  of  healthy 
subjects  at  the  same  age.  For  purposes  of  com- 
parison the  quantities  of  uric  acid  found  by  him 
were  calculated  in  grammes  per  100  kilogrammes 
of  the  body-weight.  His  results  are  given  in  the 
following  table  : — 


Age. 

Gouty  subject. 

Healthy  subject. 

30  to  40 
40  to  50 
50  to  60 
60  to  70 

0-885  grm. 
0-818     „ 
0-701     „ 
0-661     ,, 

0-965  grm, 
0-882     „ 

0-752     „ 

This  table  indicates  that  the  amounts  of  uric 
acid  excreted  by  gouty  subjects  were  always  rather 
lower  than  the  quantities  excreted  by  healthy 
persons  of  the  same  age. 

Dr.  John  Fawcett  f  also  found  as  the  result 
of  several  careful  determinations  of  the  uric  acid 
elimination  of  various  gouty  patients  that,  in  the 
majority  of  cases,  the  amounts  excreted  were 
distinctly  below  the  average  uric  acid  excretion 
of  a  healthy  man  on  similar  diet. 

In  the  following  table  (Table  I.)  are  the  results 

*  Berliner  klinische  JVochenschrlft,  1892,  p.  413. 
t  "  Guy's  Hospital  Eeports,"  1895. 


28 


The  Pathology  of  Gout. 


of  the  daily  determinations  that  I  made  for  eight 
successive  days  respectively  of  the  total  uric  acid 
excretion  in  the  urine  of  three  persons,  viz. : — 
(a)  A  male  patient  suffering  from  an  attack  of 
subacute  gout  supervening  on  chronic  gout ; 
(6)  a  male  patient  suffering  from  chronic  gout 
and  lead-poisoning,  with  recent  pain  in  the  right 
metatarso-phalangeal  joint,  and  in  both  ankle 
joints;  (c)  a  healthy  man.  The  quantities  of 
uric  acid  in  the  three  cases  are  given  in  grammes, 
and  are  calculated  per  100  kilogrammes  of  the 
body-weight.  All  the  individuals  were  between 
forty  and  fifty  years  of  age. 


TABLE    I. 

Shoxcing  the  dally  elimination  of  uric  acid  in  {a)  a  case  of  subacute 
gout  ;  (ft)  a  case  of  chronic  gout  and  plunibism  ;  (c)  a  healthy 
person.  Quantities  of  uric  acid  given  in  grammes  per  100  Jiilo- 
grammes  of  the  body-weight.  AH  the  individuals  between  forty 
and  fifty  years  of  age. 


Subacute  gout. 

Chronic 

gout. 

Healthy 

subject. 

0-260 

grm. 

0-578 

grm. 

1105 

grm. 

0-263 

0-617 

1-027 

)> 

0-315 

0-665 

1-020 

>» 

0-350 

0-715 

1-376 

5' 

0-442 

0-443 

1-175 

)» 

0-556 

,, 

0-372 

1030 

■>1 

0-506 

0-593 

1-252 

>> 

0-494 

0-594 

1-203 

)> 

0-398 

»» 

0-572 

55 

1-148 

>» 

(average) 

(a^'erage) 

(average) 

These  results  probably  justify  the  view  that 
deficient  excretion  of  uric  acid  occurs  in  connec- 
tion with  gout.     Later  the  probable  role  taken  by 


Estimation  of  Uric  Acid.  29 

the  kidneys  in  the  production  of  uric  acid  and 
in  the  development  of  gout  will  be  dealt  with 
in  detail. 

ESTIMATION    OF   URIC    ACID    IX    URINE. 

One  of  the  lines  of  investigation  that  I  have  pur- 
sued required  that  a  very  large  number  of  estima- 
tions of  the  total  amount  of  uric  acid  excreted  in 
the  urine  per  diem  should  be  made.  The  process 
that  I  have  employed  throughout  is  the  Gowland- 
Hopkins  method,  which  is  a  very  accurate  and 
reliable  process.  I  have  had  a  very  considerable 
practical  experience  of  the  various  methods  that 
have  been  ejnployed  for  the  estimation  of  uric 
acid  in  the  urine,  including  Heintze's  process, 
Haycraft's  process,  Fokker's  process,  Salkowski's 
process,  and  Ludwig's  modification  of  Salkowski's 
process.  In  connection  with  all  these  processes 
there  are  faults  or  objections  from  Avhich  the 
Gowland-Hopkins  process  is  free.  This  process 
depends  upon  the  i'act  that  when  urine  is  saturated 
Avith  ammonium  chloride  all  the  uric  acid  is 
precipitated  as  an  ammonium  urate.  From  the 
ammonium  urate  the  uric  acid  is  set  free,  and 
the  amount  of  it  is  determined  bv  titration  with 
a  standard  solution  of  potassium  permanganate. 
One  great  advantage  of  this  process  is  that  there 
is  no  danger  of  the  reduction  of  the  ammonium 
urate  as  there  is  of  the  silver  urate  produced  in 
some  of  the  other  processes;  moreover,  the 
ammonium  urate  is  easy  to  filter,  and  permits 
of    ths    liberation    of    its   uric    acid    with    orreat 


30  The  Pathology  of  Gout, 

readiness.  Another  great  advantage  of  the  pro- 
cess is  that  although  xanthin  is  at  first  precipitated 
along  with  the  ammonium  urate,  yet  the  subse- 
quent treatment  with  hydrochloric  acid  entirely 
removes  it,  so  that  finally  it  is  not  estimated 
along  with  the  uric  acid. 

THE   GOWLAND-HOPKINS   METHOD    FOR   THE 
ESTIMATION    OF   URIC   ACID   IN   URINE. 

To  100  c.c.  of  the  urine  powdered  ammonium 
chloride  is  added  till  practical  saturation  is  ob- 
tained ;  about  30  grammes  of  ammonium  chloride 
as  a  rule  are  required.  When  a  small  quantity 
remains  undissolved,  after  brisk  stirring  for  a  few 
minutes,  saturation  is  sufficiently  complete.  The 
urine  is  then  allowed  to  stand  for  two  hours, 
during  which  time,  if  possible,  it  is  occasion- 
ally stirred  to  promote  subsidence,  and  is  then 
filtered  through  thin  filter-paper,  and  washed 
three  or  four  times  with  a  saturated  solution  of 
ammonium  chloride.  The  filtrate  should  remain 
perfectly  clear  and  bright.  The  precipitated 
ammonium  urate  is  then  washed  off  the  filter  into 
a  small  beaker  with  a  jet  of  hot  distilled  water,  and 
is  heated  just  to  boiling  with  an  excess  of  hydro- 
chloric acid.  The  beaker  and  its  contents  are 
allowed  to  stand  in  the  cold  for  two  hours,  when 
the  uric  acid  separates  out  completely,  and  is  then 
collected  on  a  filter  and  washed  with  cold  distilled 
water.  The  filtrate  should  be  measured  before  the 
washing'  is  befj^un,  and  one  millii^ramme  added  to 
the  final  result  for  each  15  c.c.  of  filtrate  present — 


Estimation  of  Uric  Acid.  31 

this  need  never  be  more  than  20 — 30  c.c.  The  uric 
acid  is  then  washed  off  the  filter  with  hot  water, 
warmed  with  sodium  carbonate  till  dissolved,  and 
made  up  with  water  to  100  c.c.  The  liquid  is  then 
transferred  to  a  flask,  20  c.c.  of  strong  pure  sulphuric 
acid  are  added,  and  the  mixture  is  then  imme- 
diately and  while  warm  titrated  with  one-twentieth 
normal  potassium  permanganate  solution.  The 
latter  should  be  added  slowly  towards  the  end  of 
the  reaction,  the  close  of  which  is  marked  by  the 
first  appearance  of  a  pink  colour,  which  is  per- 
manent for  an  appreciable  interval.  Previously 
the  disappearance  of  the  colour  is  instantaneous. 
The  permanganate  solution  is  made  by  dissolving 
1*578  gramme  of  pure  potassium  permanganate  in 
a  litre  of  distilled  water.  1  c.c.  = -00375  gramme 
of  uric  acid. 

ESTIMATION    OF   URIC   ACID    IX   BLOOD. 

Another  line  of  investigation  that  I  have  pursued 
has  involved  the  examination  of  the  blood  of  man 
and  of  several  of  the  lower  animals  for  the  presence 
of  uric  acid.  Quantitative  determinations  of  uric 
acid  in  blood  have  been  made  within  the  last  few 
years  by  Salkowski  and  Leube,  von  Jaksch,  and 
Klemperer.  Salkowski  and  Leube  ^  slowly  added 
the  fluid  blood  to  ten  times  its  volume  of  boiline 
water,  boiled  for  ten  minutes,  allowed  to  subside, 
filtered,  and  evaporated  down  to  the  volume  of  the 
original  blood  used.  The  uric  acid  was  then  deter- 
mined  in   this  liquid  by  the  Salkowski   method. 

*   ''  Die  Lclire  von  K  irn,'"  p.  94. 


22  The  Pathology  of  Gout. 

Von  Jaksch  ^  diluted  the  blood  (using  from 
100 — 300  c.c.)  with  from  three  to  four  times  its 
volume  of  water  on  the  water-bath,  and  when 
coagulation  commenced  acetic  acid  was  added  so 
as  to  produce  weak  acidity ;  the  mixture  was  then 
heated  on  the  water- bath  for  15 — 20  minutes  till 
the  albumen  settled,  and  was  then  filtered,  and  the 
sediment  extracted  and  washed  with  hot  Avater. 
The  filtrate  was  further  acidified  with  acetic  acid, 
boiled,  cooled,  filtered,  and  sodium  phosphate 
added.  The  Salkowski-Ludwig  method  for  the 
estimation  of  uric  acid  was  then  employed. 
Klemperer  f  diluted  the  blood  with  from  six  to 
eight  times  its  volume  of  water,  removed  the  albu- 
men by  Von  Seegen's  method,  and  then  estimated 
the  uric  acid  by  the  Salkowski-Ludwig  process. 

In  order  to  test  the  accuracy  of  the  different 
methods  for  the  estimation  of  uric  acid  in  blood, 
a  quantity  of  fresh  bullock's  blood — which  I  proved 
to  be  free  from  uric  acid  by  the  murexide  test — 
was  taken,  and  to  it  a  known  percentage  of  uric 
acid  was  added.  I  then  experimentally  tried  on 
different  batches  of  this  blood  the  various  methods 
that  have  just  been  described.  I  obtained,  how- 
ever, such  very  erroneous  and  discordant  results 
that  I  was  forced  to  the  conclusion  that  no  reliable 
process  had  as  yet  been  devised  for  the  estimation 
of  uric  acid  in  blood.  I  therefore  endeavoured  to 
devise  a  process  that  would  yield  reliable  results. 

*  "  Ueber  die  klinisohe  Bedeutung :  Von  Harnsaure  und 
Xanthinbasen  im  Blut,"  1891. 

t  Deutsche  mediciniache  Wochenschr'tft,  1895,  xxi.,  p.  655. 


Estimation  of  Uric  Acid.  33 

After  performing  a  very  large  number  of  experi'- 
ments,  into  the  details  of  which  it  is  unnecessary 
to  go,  I  arrived  at  the  following  process,  which 
constitutes  the  most  reliable  one  i*si  the  estimation 
of  uric  acid  in  blood  with  which  I  am  acquainted. 

PUOCESS    FOR   THE   ESTIMATION    OF   URIC    ACID 
IN    RLOOD, 

The  fresh  blood  is  allowed  to  flow  direct  into 
its  own  volume  of  rectified  spirit,  with  which 
it  is  thoroughly  agitated;  the  mixture  is  then 
evaporated  on  the  water-bath  until  the  mass  can 
be  reduced  to  a  coarse  powder,  which  is  dried  in 
the  water-oven  and  afterwards  finely  powdered. 
The  admixture  of  the  blood  with  the  spirit  pre- 
cipitates the  albuminous  matters  in  a  granular 
form,  so  that  when  dried  the  blood  can  be  reduce  1 
with  ease  to  a  fine  powder.  For  the  experimental 
work  one  part  of  the  dried -blood  is  taken  as  being 
equal  to  five  parts  of  liquid  blood.  For  the  ex- 
traction and  estimation  of  uric  acid  in  blood 
from  50 — 100  grammes  of  the  powdered  blood 
should,  if  possible,  be  taken.  In  all  my  analyses  of 
the  blood  of  animals  and  birds  I  employed  100 
grammes  of  the  dried  blood,  and  in  my  analyses  ot 
human  blood  I  used  50  grammes  of  dried  blood. 
The  method  employed  was  to  mix  100  grammes  ot 
the  powdered  blood  with  a  litre  of  boiling  distill^ 
water,  and  to  allow  the  mixture  to  boil  for  half  an 
hour,  during  which  time  it  was  frequently  agitated. 
It  was  then  filtered  firstly  through  glass-wool,  and 
afterwards   through   filter   paper,   and   evaporated 


34  The  Pathology  of  Gout. 

down  to  50  c.c. ;  this  liquid  was  filtered,  allowed  to 
cool,  and  then  submitted  to  the  Gowland-Hopkins 
process  for  the  estimation  of  uric  acid.  On  adding 
known  quantities  of  uric  acid  to  different  specimens 
of  blood — which  I  had  previously  proved  to  be 
free  from  uric  acid  by  the  murexide  test — and  then 
submitting  them  to  this  process,  I  was  able  to 
extract  from  80-87  per  cent,  of  the  uric  acid,  but 
the  whole  of  the  uric  acid  could  never  be  extracted 
from  the  blood  residue.  Various  solvents  were  tr'ed 
in  place  of  the  distilled  water,  such  as  dilute 
solutions  of  sodium  acetate,  potassium  acetate, 
sodium  phosphate,  borax,  sodium  carbonate,  etc., 
in  the  hope  of  being  able  to  extract  all  the  uric 
acid  from  the  blood,  but  I  was  unable  to  find  any 
solvent  that  acted  better  than  the  distilled  water. 
This  process  that  has  just  been  described  is  the 
one  that  I  employed,  in  conjunction  with  the 
murexide  test,  in  all  the  examinations  of  the 
various  kinds  of  blood  for  uric  acid,  which  will  be 
subsequently  referred  to. 

THE   SOURCES   OF   URIC    ACID. 

Admitting  then  an  excess  of  uric  acid  in  the 
blood  in  the  form  of  quadriurate  or  biurate,  and 
that  its  deposition  therefrom  as  the  sodium  biurate 
in  cartilages  and  other  tissues  is  the  direct  exciting 
cause  of  a  gouty  paroxysm,  the  two  questions 
that  naturally  arise  are  :  (1)  Where  is  the 
uric  acid  formed  ?  (2)  How  is  the  uric  acid 
formed  ?  I  believe  that  uric  acid  is  formed 
in   connection  with   some  diseases,  notably  blood 


Sources  of  Uric  Acid.  35 

diseases  accompanied  by  leiicocytosis,  in  a  different 
manner  to  that  in  which  it  is  produced  in 
heakh,  and  also  that  in  connection  with  such 
diseases  it  is  formed  in  different  organs  to  those 
in  which  it  is  produced  in  health.  I  also  hold 
the  opinion  that  the  source  of  the  uric  acid 
contained  in  the  blood  in  gout  is  the  same  as  that 
from  which  the  uric  acid  eliminated  in  the  urine  in 
health  is  derived.  It  will  be  well,  therefore,  first  to 
consider  the  various  views  as  to  the  seat  or  seats  of 
formation  of  uric  acid  in  health  and  in  gout. 


36 


CHAPTER  III. 

Seat  or  seats  of  formation  of  uric  acid — Uric  acid  not  a 
normal  constituent  of  the  blood — Pathological  con- 
ditions under  which  uric  acid  appears  in  the  blood. 

VIEW  THAT  THE    KIDNEYS   FORM    AS   WELL   AS 
EXCRETE   URIC   ACID. 

Until  1847  it  was  supposed  that  uric  acid 
was  formed  in  the  kidneys  themselves,  as  up 
to  that  time  none  had  ever  been  detected  in  the 
blood.  In  that  year  Sir  Alfred  Garrod  demon- 
strated the  presence  of  uric  acid  in  the  blood  of 
gouty  subjects,  which  discovery  led  to  the  con- 
clusion that  uric  acid  was  formed  in  certain  other 
organs  and  tissues  of  the  body,  and  was  merely 
eliminated  by  the  kidneys.  The  view  that  then 
arose  was  that  the  uric  acid  eliminated  in  the  urine 
originated  in  the  system  by  the  metabolism  of  the 
nitrogenised  tissues,  and  was  then  thrown  out  by 
the  kidneys.  Sir  Alfred  Garrod^  originally  held 
this  view,  but  in  later  years  he  came  to  the  con- 
clusion that  uric  acid  is  produced  by  the  direct 
action  of  the  kidneys  from  urea  and  other  nitro- 
genised bodies  contained  in  the  blood  and  con- 
veyed to  the  kidneys.  From  the  experimental 
evidence   that   he   has    })ut    forward,    Sir    Alfred 

♦  "  Transactions  of  the  Koyal  Medical  and  Chirurgical  Society," 
1848,  p.  93. 


The  Kidneys  and  Uric  Acid,  37 

Garrod*  concludes  that  the  presence  of  the  salt  of 
uric  acid  in  the  blood  of  gouty  subjects,  provided 
it  is  not  introduced  via  the  alimentary  canal,  must 
be  accounted  for  by  absorption  into  the  blood  from 
the  kidneys  after  its  formation  in  these  organs,  the 
salt  being  changed  by  the  blood  from  ammonium 
quadriurate,  which  is  the  form  in  which  uric  acid 
is  mainly  present  in  the  kidneys,  to  sodium  quadri- 
urate, which  is  the  form  in  which  uric  acid  first 
appears  in  the  blood.  He  therefore  concludes 
that  uric  acid  is  normally  formed  in  the  kidneys, 
and  that  when  present  in  the  blood  it  is  a 
result  of  its  having  been  absorbed  after  forma- 
tion in  those  or^-ans.  Kolischf  resrards  the 
kidneys  as  the  most  important  of  the  uric  acid- 
forming  organs.  Dr.  Latham  considers  that  the 
final  formation  of  uric  acid  takes  place  in  the 
kidneys,  where  it  is  produced  by  the  conjugation  of 
substances  manufactured  in  the  liver,  and  conveyed 
in  the  blood  to  the  kidneys. 

The  following  experimental  evidence  has  been 
put  forward  in  support  of  the  view  that  uric  acid 
is  formed  in  the  kidneys.  Zalesky  experimented 
on  serpents,  who  eliminate  all  their  urinary 
nitrogen  as  uric  acid.  He  found  that  after  re- 
moval of  the  kidneys  of  serpents  they  lived 
about  as  long  a  time  as  when  the  ureters  were 
tied,  and  that  after  death  no  uratic  deposits 
were  found  in  any  of  the  tissues.  As  he  found 
after  ligaturing  the  ureters  of  other  serpents  that 

*  ''  Proceedings  of  the  Rojal  Society,"  1893,  pp.  482-484. 
f   Wiener  klinlscke  Woelxenschrift,  1895,  viii.,  p.  787. 


38  The  Pathology  of  Gout. 

uratic  deposits  were  to  be  seen  after  death  in  most 
of  the  organs  and  tissues,  he  concluded  that  the 
kidneys  were  the  producers  as  well  as  the  elimi- 
nators of  uric  acid.  The  following  experiments 
also  are  strongl}^  opposed  to  the  view  that  the 
kidneys,  with  regard  to  uric  acid,  merely  act  as 
filters,  which  separate  the  uric  acid  brought  to  them 
in  the  blood.  Sir  Alfred  Garrod  ^  gave  from  fifteen 
to  thirty  grains  of  potassium  urate  daily,  and  similar 
daily  doses  of  sodium  urate,  without  producing  any 
increase  of  uric  acid  in  the  urine.  Wohler  and 
Frerichs  found  that  the  administration  of  potas- 
sium and  sodium  urates  increased  the  amount  of 
urea,  but  did  not^  augment  the  quaiitity  of  uric  acid 
■in  the  urine^_  Neubauer  found  that  the  adminis- 
tration of  large  quantities  of  uric  acid  to  rabbits, 
either  by  the  stomach  or  by  injection  into  the  veins, 
was  followed  by  a  corresponding  increase  in  the 
excretion  of  urea,  but  no_uric  acid  was  discovered 
in  the  urine.  ^' 

VIEW   THAT   THE   LIVER   AND   SPLEEN    PRODUCE 
URIC   ACID. 

The  view  that  the  liver  was  the  seat  of  pro- 
duction of  uric  acid  probably  originated  in  the 
knowledge  that  the  excretion  of  uric  acid  in  the 
urine  is  most  abundant  during  digestion,  when  the 
liver  is  most  active.  This  view  is,  however,  equally 
compatible  with  the  idea  that  the  liver  merely 
produces  the  antecedents  of  uric  acid,  which  sub- 
sequently become  conjugated  in  the  kidneys.     The 

*  "  Lumleian  Lectures,"  1883. 


The  Liver  and  Uric  Acid.  39 

investigations  of  Schrijcler  and  Minkowski  ap- 
parently were  strongly  in  favour  of  the  view  that 
uric  acid  was  formed  in  the  liver.  Schroder  ^ 
states  that  the  liver  of  birds  contains  a  high  per- 
centage of  uric  acid,  and  that  after  removal  of  the 
kidneys  uric  acid  continues  to  be  formed,  and 
accumulates  in  the  liver  and  blood.  The  lasl- 
nientioned  statement  is  utterly  opposed  to  the 
results  of  Zalesky's  experiments  on  the  extirpation 
of  the  kidneys  of  serpents.  Moreover,  if  the  liver 
of  birds  contained  uric  acid,  and  if  it  passed  thence 
to  the  kidneys,  it  nmst  be  present  in  the  blood. 
As  will  be  shoAvn  by  and  by,  the  blood  of  birds  is 
quite  free  from  uric  acid.  Minkowski  f  succeeded 
in  keeping  geese  alive  from  six  to  twenty  hours 
after  extirpation  of  the  liver ;  after  the  opera- 
tion, their  urinary  excrement  contained  only  2  to 
3  per  cent.  oP  uric  acid,  instead  of  the  normal 
60  or  70  per  cent.  This  diminished  excretion  of 
uric  acid  after  extirpation  of  the  liver  is,  however, 
no  proof  that  the  liver  is  the  seat  of  formation  of 
uric  acid.  The  results  are  equally  compatible  with 
the  view  that  the  liver  is  the  seat  of  production  of 
the  antecedents  of  uric  acid  only. 

Dr.  Murchison  regarded  the  liver  as  the  seat  of 
production  of  uric  acid,  and  considered  that  the  pre- 
sence of  the  latter  in  the  blood  or  tissues  was  due  to 
functional  derangement  of  the  liver,  in  consequence 
of  which  the  metabolism  of  some  of  the  albumen 
became  arrested  at  the  stage  of  uric  acid  formation, 

*  Lxidii-ig's  Festschrift,  1887,  p.  89. 
t  Arch.  Exp.  Fath.  ii.  FharmaJc.,  xxi. 


40  The  Pathology  of  Gout. 

instead  of  going  on  to  the  complete  stage  of  urea 
formation.  Charcot  regarded  the  liver  as  the 
principal  seat  of  production  of  uric  acid.  He 
considered  that  a  functional  derano^ement  of  the 
liver  caused  the  production  of  excessive  quantities 
of  uric  acid,  and  its  consequent  accumulation  in 
the  blood.  Meissner  regards  the  liver  of  fowls  in 
the  normal  condition  as  the  principal  source  of  uric 
acid,  but  considers  that  the  spleen  and  the  nervous 
tissues  share  in  the  formation.  Ranke  was  of 
opinion  that  his  experiments  led  to  the  conclusion 
that  the  spleen  was  the  principal  organ  concerned 
in  the  production  of  uric  acid.  It  has,  however, 
never  been  possible  to  show  that  tbe  spleen  takes 
any  active  part  in  developing  gout.  On  the  con- 
trary, the  large  amount  of  uric  acid  found  in  the 
blood  of  cases  of  leucocythsemia  and  severe  anaemia 
show  that  an  exaggerated  production  of  lu'ic  acid 
does  not  by  itself  exert  any  influence  on  the  origin 
of  gout. 

VIEWS    THAT    URIC    ACID    IS    PRODUCED    IX    VARIOUS 

TISSUES. 

Ebstein,  who  attributes  in  cases  or  gout  the 
main  production  of  uric  acid  to  the  muscles 
and  bone-marrow  of  the  affected  extremities, 
admits,  however,  that  the  kidneys  may  take  a 
part,  not  only  in  the  secretion,  but  also  in  the 
manufacture  of  uric  acid.  Robins  was  the  first  to 
formulate  the  view  that  uric  acid  is  formed  in 
connective  tissues  generally,  and  that  the  patho- 
logical condition  is  merely  an  exaggeration  of  the 


Connective  Tissues  and  Gout.         41 

physiological  one.  This  view  therefore  regards 
normal  tibrous  tissues  as  the  seat  of  production  of 
uric  acid,  and  considers  that  in  gout  this  production 
is  increased.  Chrzonsczewsky  also  concludes  that 
uric  acid  arises  in  connective  tissue,  and  that  it  is 
conducted  thence  through  the  lymphatic  vessels. 
Cantani  considers  that  the  connective  tissues  take 
an  active  part  in  the  formation  of  uric  acid,  and 
that  in  cases  of  gout  it  is  especially  produced  in  the 
cartilages  and  peri-articular  tissues  (ligaments, 
tendons,  etc.).  Senator  also  inclines  to  the  opinion 
that  at  least  part  of  the  uric  acid  is  formed  in 
cartilaofinous  tissue.  Most  writers  and  observers 
on  the  subject,  however,  consider  that  it  is  only 
certain  that  uric  acid  deposits  in  substances 
of  the  connective- tissue  class,  and  that  there 
is  no  proof  that  uric  acid  is  formed  in  connective 
tissue. 

Dr.  Haio-  claims  that,  in  addition  to  the  forma- 
tion  of  uric  acid  in  the  animal  economy,  the  gradual 
introduction  of  small  quantities  of  uric  acid  in 
the  food  leads  to  its  gradual  accumulation,  and 
that  consequently  very  large  amounts  may  be 
stored  m  the  body  without  any  excessive  formation 
having  taken  place.  Dr.  Haig,  however,  does  not 
produce  any  proof  that  uric  acid  is  stored  up  in 
the  system  apart  from  gout.  The  contrary  is 
proved  by  the  fact  that  in  diseases  such  as  leuco- 
cythiemia,  severe  anoemia,  etc.,  although  large 
quantities  of  uric  acid  are  formed,  yet  they  are 
readily  eliminated  without  storage  in  the  system 
occurrinsf. 


42  The  Pathology  of  Gout. 

is  uric  acid  a  normal  constituent  of 
the  blood? 

It  will  be  evident  that  if  the  various  views 
as  to  the  formation  of  uric  acid  in  the  liver, 
spleen,  connective  tissues,  muscles,  and  bone- 
marrow  be  correct,  then  it  must  be  conveyed  in 
the  blood  in  order  to  be  excreted  by  the  kidneys. 
We  know  that  some  400-500  grains  of  urea  are 
normally  excreted  in  the  urine,  and  that  this  urea 
is  convej^ed  in  the  blood  from  various  organs  to 
the  kidneys,  where  it  is  excreted.  But,  in  addition, 
from  eight  to  ten  grains  of  uric  acid  are  daily 
excreted  in  the  urine  of  man.  The  question  is. 
Does  this  uric  acid  come  as  such  to  the  kidneys  ? 
In  other  words,  is  it  produced  in  any  of  the  organs 
or  tissues  of  the  body  generally  and  conveyed 
in  the  blood  to  the  kidneys,  to  be  by  them  excreted, 
or  is  it  produced  in  the  kidneys  and  then  turned 
into  the  urine  ?  The  answers  to  these  questions 
will  depend  very  much  upon  our  ascertaining 
whether  uric  acid  exists  in  the  blood  of  man  in 
health,  and  whether  it  exists  in  the  blood  of  those 
animals,  such  as  birds,  the  whole  of  whose  nitro- 
genous urinary  excrement  consists  of  a  compound 
of  uric  acid.  For  it  follows  that  if  uric  acid  be 
not  formed  in  the  kidneys,  it  must  be  conveyed 
in  the  blood  to  those  organs.  If  such  be  the  case, 
its  detection  in  the  blood,  provided  careful  search 
for  it  be  made,  ought  to  be  a  fairly  easy  matter, 
considering  that  in  the  murexide  reaction  we 
have    such    an   extremely   delicate    test   for    the 


The  Blood  in  Health,  43 

identification  of  uric  acid.  Here  it  is  well  to 
bear  in  mind  that  statements  as  to  the  presence 
of  uric  acid  in  the  blood  and  viscera  are  valueless 
unless  the  substance  is  proved  to  be  uric  acid 
by  the  nnirexide  test.  Dr.  Haig,  who  asserts  that 
uric  acid  is  always  present  in  the  blood  and  tissues, 
bases  his  statements  solely  on  the  application  of 
Haycraft's  process  to  water-extracts  of  the  blood 
and  tissues,  and  the  subsequent  calculation  of 
the  silver  precipitate  so  obtained  in  terms  of  uric 
acid.  As  far  as  can  be  ascertained  from  Dr.  Haig's 
Avritings,  he  has  never  identified  by  the  murexide 
test  this  uric  acid  reported  to  be  present  in  the 
blood  and  tissues. 

URIC   ACID    NOT   PRESENT    IN   THE   BLOOD   OF   MAN 
IN    HEALTH. 

Sir  Alfred  Garrod,^  as  the  result  of  his 
investigations,  declares  that  in  absolute  health 
the  uric  acid  in  the  blood  is  inappreciable,  that 
in  gout  the  blood  is  very  rich  in  it,  and  that 
uric  acid  is  found  in  smaller  but  appreciable 
quantities  in  individuals  who  are  developing  a 
gouty  condition,  or  who  are  under  the  poisonous 
influence  of  lead.  Yon  Jaksch  f  examined  the 
blood  of  several  healthy  individuals,  but  found  no 
uric  acid  present.  Klemperer  :|:  also  was  unable 
to  find  any  uric  acid  in  the  blood  of  healthy 
persons.  I  have  also  carefully  examined  the 
blood  of  healthy  subjects  by  the  process  previousl}' 

*  "Lumleian  Lectures,"  1883. 

t  Deutsche  inedicinische  Wochenschrift,  1890,  xxxiii.,  p.  7-11. 

\  Lentsche  medic'uusche  Wochenschrift,  1895,  xxi.,  p.  Goo. 


44  The  Pathology  of  Gout. 

described,  and  have  been  unable  to  find  any  uric 
acid  present.  On  the  other  hand,  urea  was  found 
in  every  sample  of  blood  examined. 

URIC   ACID    NOT   PRESENT   IN   THE   BLOOD   OF 
MAMMALS    OTHER   THAN    MAN. 

Sir  Alfred  Garrod*  examined  the  blood  of 
the  ox,  sheep,  and  pig  by  the  uric  acid  thread 
test,  but  could  never  find  a  trace  of  uric  acid 
present.  I  have  also  examined  the  blood  of  the  ox 
and  sheep,  working  on  very  large  quantities  of 
blood  by  the  process  I  have  described,  but  I  have 
never  found  any  uric  acid  present.  On  the  other 
hand,  urea  was  found  in  every  sample  of  blood 
examined. 

URIC   ACID   NOT   PRESENT   IN   THE   BLOOD   OF 
BIRDS   AND   REPTILES. 

The  examination  of  the  blood  of  birds  and 
reptiles  has  a  very  important  bearing  on  the 
discovery  of  the  normal  seat  of  formation  of 
uric  acid.  As  is  well  known,  the  semi-solid 
urinary  excrement  of  birds  consists,  apart  from 
the  small  quantity  of  water  present,  entirely  of 
uric  acid  compounds,  so  that  the  nitrogen  excreted 
by  the  kidneys  of  birds  is  eliminated  entirely  in 
the  form  of  uric  acid  and  none  of  it  in  the  form 
of  urea.  This  white  mortar-like  urinary  excrement 
of  birds  has  been  shown  by  Sir  William  Roberts 
to    consist    of    the    quadriurates    of   ammonium, 

*  "  Lumleian  Lectures,"  1883. 


The  Blood  of  Birds.  45 

potassium,  and  sodium.  Consequently  birds  excrete 
in  proportion  to  their  body-weight  an  enormous 
amount  of  uric  acid  as  compared  with  the  uric 
acid  output  of  mammals.  If  this  large  quantity 
of  uric  acid  be  produced  in  the  organs  and  tissues 
generally  it  must  be  conveyed  in  the  blood  to 
the  kidneys,  and  it  therefore  would  be  easy 
of  detection  in  the  blood  of  birds.  Now  it  can 
be  demonstrated  that  the  blood  of  birds  is  abso- 
lutely free  from  uric  acid. 

Sir  Alfred  Garrod  examined  the  blood  of  the 
turke}^,  fowl,  pigeon  and  duck  by  the  uric  acid 
thread  test,  but  never  found  a  trace  of  uric  acid 
present.  I  considered  that  these  observations 
of  Sir  Alfred  Garrod  as  to  the  absence  of  uric 
acid  from  the  blood  of  birds  were  of  so  great 
importance — in  view  of  the  opinion  which  I  strongly 
entertain  that  uric  acid  in  health  is  only  formed 
in  the  kidneys — that  I  thought  it  desirable  to 
re-examine  the  blood  of  birds.  I  accordingly 
worked  on  very  large  quantities  of  the  blood  of 
the  turkey,  goose,  duck  and  fowl.  After  the  most 
careful  examination,  I  have  never  been  able  to 
detect  any  uric  acid  in  the  blood  of  these  birds, 
and  I  therefore  confirm  Garrod's  observations. 
I  am  also  able  to  confirm  his  observations  as  to 
the  presence  of  urea  in  the  blood  of  birds.  I  found 
urea  present  in  the  blood  of  all  the  birds  that  I 
examined,  viz.  the  turkey,  goose,  duck  and  fowl. 

Dr.  John  Davy  examined  the  blood  of  two 
snakes  {vijyev  communis)  for  uric  acid,  but  failed 
to  detect  any. 


4.6  The  Pathology  of  Gout. 

The  objection  has  been  raised  to  the  above- 
mentioned  experiments  that  the  quantity  of  uric 
acid  present  in  the  blood  requisite  to  produce 
a  daily  excretion  of  eight  to  ten  grains  might 
be  so  minute  as  to  escape  detection.  This  objec- 
tion, I  think,  is  disposed  of  by  the  fact  that 
I  have  worked  on  pints  of  mammalian  blood  at 
a  time,  and  have  not  been  able  to  extract  the 
least  trace  of  uric  acid,  although  urea  was  always 
found.  That  the  process  was  a  reliable  one  was 
shown  by  the  fact  that  when  I  purposely  added 
small  quantities  of  uric  acid  to  either  mammalian 
blood  or  birds'  blood  I  could  always  easily  extract 
it  and  detect  its  presence.  Moreover,  the  objection 
as  to  the  supposed  difficulty  of  detecting  small 
quantities  of  uric  acid,  if  such  were  normally 
present  in  blood,  is  not  a  valid  one,  considering 
that  in  the  murexide  test  for  uric  acid  we  have 
a  test  of  extreme  delicacy.  It  can  be  demon- 
strated {see  p.  3)  that  the  one-hundredth  part  of 
a  milligramme  of  uric  acid  gives  a  very  evident 
murexide  reaction.  However,  the  objection  that 
has  been  raised  could  not  possibly  apply  to  the 
examination  of  the  blood  of  birds.  The  urinary 
excrement  of  birds  consists  almost  entirely  of 
compounds  of  uric  acid  and  contains  no  urea, 
and  if  such  uric  acid  is  conveyed  by  the  blood 
to  the  kidneys,  then  it  must  be  capable  of  easy 
detection  in  that  medium.  Yet,  as  previously 
mentioned,  no  uric  acid  can  be  detected  in  the 
blood  of  birds. 

This    mass    of    experimental   evidence,   which 


Sources  of  Uric  Acid.  47 

shows  that  uric  acid  is  never  present  in  the  blood 
of  human  beings  and  of  other  mammals  in  health, 
and  also  that  it  is  never  present  in  the  blood  of 
birds  and  serpents,  although  their  urinary  excre- 
tion is  almost  entirely  composed  of  a  compound 
of  uric  acid,  conclusively  supports  the  view  that 
uric  acid  is  normally  produced  in  the  kidneys. 
How  is  it  possible  in  all  these  cases  that  uric 
acid  could  be  absent  from  the  blood,  if  the  view 
be  correct  that  uric  acid  is  formed  in  the  system 
generally,  and  is  conveyed  in  the  blood  to  the 
kidneys,  which  play,  as  it  were,  merely  the  part 
of  a  filter  in  the  removal  of  the  uric  acid  from 
the  blood  ?  I  consider  that  the  evidence  brought 
forward  renders  such  a  view  impossible. 

THE  SOURCES  AND  FORMATTOJ^  OF  URIC  ACID  IN 
PATHOLOGICAL  CONDITIONS,  OTHER  THAN  GOUT, 
IN   WHICH   IT   APPEARS   IN   THE   BLOOD. 

Although  I  hold  the  opinion  that  in  health 
uric  acid  is  onl}^  formed  in  the  kidneys,  and 
that  the  uric  acid  found  in  the  blood  in  gout 
is  absorbed  from  the  kidneys  after  formation  in 
these  organs,  yet  it  must  be  borne  in  mind 
that  there  are  other  diseases,  besides  gout,  in 
which  uric  acid  appears  in  the  blood,  and  in 
connection  with  which  it  has  most  probably  not 
been  absorbed  from  the  kidneys,  but  has  been 
formed  elsewhere  in  the  system.  It  will,  therefore, 
be  w^ell  briefly  to  consider  what  these  pathological 
conditions  are,  and  what  are  the  probable  sources 
of  the  uric  acid  in  such  conditions.     The  investi- 


48  The  Pathology  of  Gout. 

gations  of  Yon  Jaksch,  Klemperer,  and  others 
have  condusively  established  that  the  presence 
of  uric  acid  in  the  blood  is  not  a  pathognomonic 
sign  of  gout,  and  also  that  uric  acid  may  appear 
in  quantities  in  the  blood,  and  be  ehminated 
without  causing  gout. 

BLOOD   DISORDERS   ACCOMPANIED   BY   THE  PRESENCE 
OF    URIC   ACID    IN   THE   BLOOD. 

Yon  Jaksch^  found  uric  acid  in  the  blood 
of  cases  of  both  primary  and  secondary  ana?mia, 
pernicious  anaemia,  and  splenic  tumour.  He 
also  found  it  in  the  blood  in  conditions  in- 
ducing dyspnoea,  notably  in  heart  disease,  pleurisy 
with  effusion,  pulmonary  catarrh,  pneumonia,  and 
emphysema.  Klemperer  t  has  recently  confirmed 
the  results  of  Yon  Jaksch  and  others  as  to 
the  presence  of  uric  acid  in  the  blood  of  leuco- 
cythiemia,  and  many  observations  have  been 
made  of  the  increased  excretion  of  uric  acid 
that  accompanies  this  disease.  Laache  %  found 
a  daily  excretion  of  3-7  grammes  (nearly  six 
t'mes  the  average  normal  amount)  in  a  patient 
s  iffering  from  this  disease.  Bartels  §  observed 
a  daily  excretion  of  4  grammes  (more  than  six 
times  the  average  normal  amount).  Stadthagen  || 
found  a  daily  excretion  of  2  grammes  (three  times 
the     average    normal     amount).       Bohland     and 

'  *  Deutsche  meiVxcmuche  Wochem^chriff,  1890,  xxxiii.,  p.  741 

t  Deutsche  incdicinische  Jf'ofhenschr{ft,  1895,  xxi.,  p.  655. 
J  "  Klinische  Urinanalysc,"  1892,  p.  31. 
§  Deutsche  Archivfiir  klinische  Mediciv,  Pand  i.,  p.  13. 
II  J'jjT^ic/M'*  ^m'Jw,  Bandcix.,  p.  390. 


Sources  of  Uric  Acid.  49 

Scherz  ^  found  a  daily  excretion  of  1*4  gramme 
(twice  the  average  normal  amount).  Von  Jaksch  t 
concluded  that  the  occurrence  of  uric  acid  in 
the  blood  was  due  to  diminution  of  the  oxidising 
activity  of  the  red  corpuscles,  and  to  consequent 
storing  up  in  the  blood  of  the  uric  acid  formed 
in  the  body,  which,  according  to  his  view,  is 
normally  oxidised  and  destroyed.  Horbaczewski's 
view,  which  will  be  considered  later,  that  the 
formation  of  uric  acid  is  due  to  the  disintegration 
of  leucocytes  would  equally  apply,  since  in  all 
the  diseases  in  which  Yon  Jaksch  found  uric 
acid  in  the  blood,  leucocytosis  was  present.  More- 
over, there  is  no  experimental  proof  to  support 
the  view  that  uric  acid  is  oxidised  and  destroyed 
by  oxygenated  blood.  On  the  contrary,  there 
is  experimental  proof  that  the  process  of  oxy- 
genation can,  in  the  presence  ot  nuclein,  produce 
uric  acid  instead  of  destroying  it. 

RENAL    DISEASES    ACCOMPANIED    BY    THE    PRESENCE 
OF   URIC   ACID   IN   THE   BLOOD. 

Yon  Jaksch  J  found  uric  acid  in  the  blood 
of  all  the  cases  of  renal  disease  that  he  examined, 
the  proportions  being  especially  large  in  cases  of 
granular  kidney  disease  and  uraemia.  Yon  Jaksch's 
results  were  confirmed  by  Klemperer,§  who  ex- 
amined the  blood  of  cases  of  contracted  kidney,  and 

*  Tfluger'^s  Archii',  Band  xlvii.,  p.  13. 

f  "Ueber    die    klinische    Bedeutung.     Yon    Harnsiiure    und 
Xanthinbasen  im  Blut,"  1890. 
X  Loc.  cit. 
§  Loc.  cit. 


50  The  Pathology  of  Gout. 

found  uric  acid  always  present.    OVfYJoncily  tliis  fur- 

,jiislies  a  further  proof  as  to  the^rmin,!  oriogn^uric 

acid^  when  it  can  be  shown  that  in  such  cases  of 


■l-i(ipp.y  rjispnsft  (nat  associated  with  gout)  in  which 
^the   uric   acid  excretion  is  diniinished,  uric   acid 
.    lY^al-Ac;  jj;.Q  appearance  in  the  blood. 

LEAD    POISONING    ACCOMPANIED    BY    THE    PRESENCE 
OF   URIC   ACID   IN   THE   BLOOD. 

Sir  Alfred  Garrod  "^  examined  the  blood  of 
nine  patients  suffering  from  plumbism,  who 
had  never  suffered  from  gout,  and  found  ap- 
preciable quantities  of  uric  acid  in  the  blood 
of  seven  out  of  the  nine.  Dr.  Oliver  t  refers 
to  the  early  stage  at  which  anoemia  becomes  a 
prominent  symptom  of  lead  poisoning.  Although 
no  doubt  the  kidney  mischief  which  occurs  in 
connection  with  plumbism  is  responsible  for  the 
appearance  of  most  of  the  uric  acid  in  the  blood, 
by  interfering  with  its  excretion  by  the  kidney 
cells,  yet  it  is  possible  that  a  small  amount  of  the 
uric  acid  may  result  from  the  sKght  leucocytosis 
accompanying  the  anaemia  of  plumbism. 

FEVERS    AND   ABSENCE    OF   URIC   ACID    FROM   THE 

BLOOD. 

Von  Jaksch  found  no  uric  acid  in  the  blood  of 
patients  suffering  from  typhoid  fever,  intermittent 
fever,  and  acute  rheumatism,  nor  in  connection 
with  diseases  of  the  liver,  stomach,  and  intestines, 
v/hen  unaccompanied  by  anaemia.    His  observations 

*  "  A  Treatise  on  Gout,"  1876,  p.  241. 

f  Goulstonian  Lectures  on  "Lead  Poisoning,"  1891. 


Sources  of  Uric  Acid.  51 

seem  unduubtedly  to  prove  that  the  presence  of 
uric  acid  in  the  blood  is  not  a  fuctor  in  the  pro- 
.  duction  of  the  so-called  uric  acid  intoxication  of 
fever.  Fever,  indeed,  appears  to  influence  un- 
favourably the  production  of  uric  acid. 

FORMATION    OF   URIC   ACID    DIFFERENT   IN   GOUT 
AND    IN   BLOOD    DISEASES. 

It  is  evident  that  in  connection  with   certain 
diseases,   especially   those    in   which    leucocytosis 
occurs,  uric   acid   in   the   form    of   sodium  quad- 
riurate    may    be    present    in    quantities    in    the 
blood,    and    yet    not    give    rise    to    gout.       The 
reason,  in  my  opinion,  is  that  in  such  diseases  the 
kidneys  being   in   a   sound  condition  can  readily 
eliminate  the  quadriurate.     I  believe  that  the  seat 
or  site  of  formation  of  uric  acid  is  a  different  one 
in  gout  to  what  it  is  in  these  blood  disorders,  in 
which  uric  acid  occurs  in  the  blood  without  the 
development  of  gout.     In   gout  I  believe  that  all 
the    uric   acid  present  in    the    blood   is   absorbed 
from  the  kidneys,  owing  to  some  affection  of  those 
organs  which    interferes  with    the   proper    excre- 
tion of  the  uric  acid  formed  in  the  kidneys.     In 
cases  of  contracted  granular  kidney  disease,  and 
in  cases  of  plumbism,  the  uric  acid  present  in  the 
blood  is,  I  believe,  derived  from  the  same  source, 
viz.  from  the  damaged  kidneys.      In  blood  diseases 
and  disorders  the  uric  acid  present  in  the  blood  is 
probably  derived  from  the  nuclein  of  the  leucocytes, 
and  as  the  kidne^^s  are  in  a  sound  condition  it  is 
readily  excreted  by  them. 


52 


CHAPTER  IV. 

The  reiial  origin  of  gout — Association  of  kidney  affections 
with  gout — Association  of  renal  disease  with  the 
presence  of  uric  acid  in  the  blood — Nature  of  the 
kidney  affection  which  causes  gout. 

ASSOCIATION    OF   KIDNEY   AFFECTIONS   WITH    GOUT. 

An  interesting  point  to  consider  is  whether  gout 
ever  occurs  without  preceding  kidney  mischief  of 
some  kind  or  other.  That  is,  whether,  if  the 
kidneys  remain  sound,  it  is  possible  for  such  an 
accumulation  of  uric  acid  to  occur  in  the  system  as 
to  produce  an  attack  of  gout.  We  will  first  ascer- 
tain whether  there  is  any  evidence  that  an  affection 
of  the  kidneys  (functional  or  organic)  is  associated 
with  or  precedes  gout.  In  the  first  place  it  is  time 
that  the  old  idea  should  be  abandoned  that  the 
healthy  kidneys  can  only  eliminate  a  certain 
amount  of  uric  acid.  That  the  healthy  kidneys 
are  capable  of  separating  from  the  blood  and  ex- 
creting large  quantities  of  uric  acid  is  shown  by 
the  observations,  previously  referred  to,  of  Laache, 
Eartels,  Stadthagen,  and  Bohland  and  Scherz,  on 
the  excretion  of  uric  acid  in  cases  of  leucocythaemia. 
In  this  disease  the  blood  is  laden  with  uric  acid, 
and  all  these  observers  found  a  greatly  increased 
daily  excretion  of  uric  acid,  varying  from  twice  to 
over  six  times  the  normal  amount.  This  large 
excretion  of  uric  acid  by  the  kidneys  shows  that 


Gout  and  Kidney  Affections,  53 

urates  do  not  themselves  cause  damage  to  the  uric 
acid-secreting  cells  of  the  kidneys. 

VIEWS   AS   TO   THE    ASSOCIATION    OF   GOUT   AND 
KIDNEY   DISEASE. 

Sir  Alfred  Garrod,  Sir  William  Roberts,  and 
Levison  all  attribute  the  accumulation  of  uric 
acid  in  the  blood  of  gouty  persons  to  deficient 
excretion  rather  than  to  increased  production. 
Sir  Alfred  Garrod  holds  the  view  that  among  the 
causes  exciting  a  gouty  fit  is  a  functional  failure  of 
eliminating  power  for  uric  acid  on  the  part  of  the 
kidneys.  He  also  considers  that  this  early  func- 
tional failure  is  followed  in  cases  of  chronic  gout 
by  structural  kidney  disease.  His  view  is  that  the 
uric  acid  present  in  the  blood  of  gout  is  formed  in 
the  kidneys,  and  is  absorbed  from  them  into  the 
blood.  This  view  is  quite  compatible  with  the 
theory  that  a  defective  capacity  of  the  kidneys  for 
the  excretion  of  uric  acid  is  the  primary  patho- 
logical cause  of  gout.  Levison  "^  states  that  gout  is 
not  accompanied  by  leucocytosis,  and  therefore  the 
nuclein  of  leucocytes  is  not  available  for  the 
production  of  uric  acid.  He  considers  that  gout 
cannot  be  developed  unless  a  primary  renal  lesion 
is  present,  and  that  this  is  almost  invariably  of  the 
nature  of  an  interstitial  change.  Yogel  t  estimated, 
in  three  cases  of  chronic  gout,  the  intake  of  nitrogen 
by  analysis  of  the  food  and  the  output  of  nitrogen 
in  the  urine  and  fa3ces.     He  found  that  there  was 

*  "The  Uric  Acid  Diathesis,"  1894. 

t  Zeitschrift  fiir  klinische  Medicin,  xxiv.,  p.  512. 


54  The  Pathology  of  Gout. 

a  nitrogen  retention  greatly  in  excess  of  what  could 
be  attributed  to  a  retention  of  uric  acid.  Vogel 
states  that  his  patients  behaved,  in  this  respect, 
like  sufferers  from  renal  disease,  although  the 
clinical  signs  of  granular  kidney  mischief  were 
wanting  in  all  the  cases.  In  connection  with  this, 
it  must  be  borne  in  mind  that  the  absence  of  the 
clinical  signs  of  disease  of  the  kidneys  does  not 
necessarily  imply  integrit}^  of  those  organs. 

ASSOCIATION  OF  llENAL  DISEASE  WITH  THE  PRE- 
SENCE OF  URIC  ACID  IN  THE  BLOOD,  AND 
WITH   URATIC    DEPOSITS    IN    THE   JOINTS. 

As  previously  mentioned,  Yon  Jaksch  found 
considerable  quantities  of  uric  acid  in  the  blood 
of  all  the  cases  of  diseases  of  the  kidneys  that 
he  examined,  and  his  results  were  confirmed 
by  Klemperer.  It  is  well  known  that  uratic 
incrustation  of  articular  cartilages  is  not  un- 
commonly found  at  the  post-mortem  examina- 
tions of  subjects  wdio  have  never  been  known 
to  suffer  from  ostensible  gout  during  life.  Drs. 
Ord  and  Greenfield^  examined  a  number  of 
bodies  in  the  post-mortem  room  for  the  existence 
of  uratic  deposits  in  the  joints,  and  the  presence 
of  kidney  disease.  Among  96  cases  presenting 
lesions  of  the  kidneys,  uratic  deposits  were  found 
in  the  joints  of  18.  Dr.  Norman  Moore,  f  who 
bases  his  observations  on  the  results  of  a  large 
number  of  post-mortem  examinations,  states  that 

*  "  Transactions  of  the  International  Medical  Congress  at 
London,  1881,"  vol.  ii.,  p.  107. 

f  "  St.  Bartholomew's  Hospital  UeporLs,  1887,"  vol.  xxiii. 


Gout  and  Kidney  Disease.  55 

chronic  interstitial  nephritis  is  found  in  a  large 
proportion  of  those  bodies  in  which  sodium  urate 
is  to  be  seen  in  the  joints.  He  found  that  chronic 
interstitial  nephritis  is  not  invariably  accompanied 
by  the  presence  of  sodium  urate  in  the  articular 
cartilages,  though  it  is  usually  accompanied  by 
some  traces  of  degeneration  in  some  of  the  articular 
cartilages.  He  examined  the  following  number 
of  cases,  all  of  which,  as  far  as  could  be  ascertained, 
had  never  suffered  from  ostensible  gout. 


Kidney  disease. 

No.  of  cases. 

Uratic  deposit  in 
joint  or  joints. 

Chronic  interstitial  nei^hritis 
Chronic  parenchymatous  ne- 
phritis 

53 
11 

25 
2 

Levison  '^  is  a  strong  supporter  of  the  view 
that  there  is  always  some  degree  of  antecedent 
renal  disease  connected  with  gout.  In  reply  to 
criticisms  of  this  view  he  points  out  that  the 
post-mortem  examinations  of  gouty  patients  have 
generally  shown  renal  lesions,  and  that  the  few 
exceptional  cases  are  open  to  criticism.  He  states 
that  all  the  post-mortem  examinations  of  patients 
dying  of  granular  kidney  disease  at  the  Communal 
Hospital,  Copenhagen,  during  a  period  of  fourteen 
months,  showed  uratic  deposits  in  one  or  other 
of  the  joints,  although  most  of  the  patients  were 
not  known  to  have  had  any  definite  gouty  attack. 
I  thought  that  it  would  be  a  matter  of  interest 
to  ascertain  the  proportion  of  cases  of  uratic 
deposition  in   the  joints  occurring  in   subjects  in 

*  Zeitschrift  fur  JcUnische  Medicin,  1894,  xxvi.,  p.  293. 


56 


The  Pathology  of  Gout. 


whom  granular  disease  of  the  kidneys  was  found 
at  the  post-mortem  examination,  and  in  connection 
with  whom  the  previous  history  as  to  the  occur- 
rence or  not  of  gout  was  known.  For  this  purpose 
I  obtained  the  help  of  some  of  the  pathologists 
at  the  London  hospitals,  who  have  kindly  examined 
the  joints  in  such  cases  whenever  they  were  able 
to  do  so.  I  have  collected  altogether  the  results 
of  77  such  examinations,  for  wdiich  I  am  indebted 
to  the  kindness  of  Dr.  Cyril  Ogle,  Dr.  F.  J.  Smith, 
Dr.  Hebb,  and  Mr.  Jackson  Clarke.  These  77 
cases  were  all  cases  of  granular  kidney  disease, 
and  in  41  cases  uratic  deposits  were  found  in 
one  or  more  of  the  joints.  The  distribution  of 
uratic  deposits  among  the  gouty  and  non-gouty 
cases  is  shown  in  the  following  table. 


TABLE  II. 

Showing  the  results  of  the  examinations  of  the  joints  of  11  cases  of 
gramdar  kidney  disease. 


Uratic  deposit  in 
joint  or  joints. 


Known  to  have  had  gout  . . . 
Never  known  to  have  had  gout 


Totals    ... 


10 
31 


41 


In  the  10  cases  known  to  have  had  gout, 
uratic  deposits  were  found  in  one  or  more  of 
the  joints  of  all,  and  the  kidney  condition  was 
in  every  case  described  as  "  markedly  granular  " 
or  "  fairly  granular." 

Among  the  67  cases  of  granular  kidney  disease 


Gout  and  Kidney  Disease.  57 

not  known  to  have  suffered  from  previous  gouty 
attacks,  uratic  deposits  Avere  found  in  one  or  more 
of  the  joints  of  31 — that  is,  in  40  per  cent,  of 
the  cases,  Avhich  closely  agrees  with  the  47  per 
cent,  found  under  similar  conditions  by  l)r. 
Norman  Moore.  In  these  67  cases  are  included 
all  cases  which  showed  the  existence  of  any 
granular  kidney  disease,  but  several  of  the  cases 
in  Avhich  no  uratic  deposits  were  found  were 
described  as  only  "  slightly  granular  "  or  ''  faintly 
granular." 

If  from  the  67  cases  a  selection  is  made  of 
those  described  as  "  markedly  granular,"  or  as 
"  typical  granular  kidneys,"  then  the  proportion 
of  cases  in  which  uratic  deposits  were  found  in 
the  joints  appears  as  follows  : — 

Uratic  deposit  in 
joint  or  joints. 


Marked      granular     kidney  \ 
disease       ...         ...         ...  j 


20 


Thus  it  is  seen  that  among  the  cases  of  marked 
granular  disease  of  the  kidneys  occurring  in  persons 
who  w^ere  never  known  to  have  suffered  from 
ostensible  gout  during  life,  uratic  deposits  were 
found  in  the  joints  of  77  per  cent,  of  the  cases. 
These  results,  taken  in  conjunction  with  those 
of  Dr.  Norman  Moore  and  of  Levison,  show  that 
kidney  disease  exercises  a  powerful  influence  in 
causing-  an  accumulation  of  uric  acid  in  the  blood, 
and  consequently  in  producing  uratic  deposits 
in  the  joints. 


58  The  Pathology  of  Gout. 

gouty  affections  of  the  kidneys  not  always 
revealed  clinically. 

It  has  been  urged  that  if  kidney  disease, 
with  the  consequent  diminished  excretion  of  uric 
acid,  be  the  primary  factor  in  the  causation  of 
gout,  signs  of  kidney  mischief  woukl  always 
manifest  themselves  prior  to  an  attack  of  gout, 
and  that  very  few  such  cases  have  ever  been 
recorded.  But,  in  the  first  place,  it  must  be 
remembered  that  such  signs  are  not  usually 
looked  for,  and,  in  the  second  place,  they  need 
not  necessarily  reveal  themselves  clinically.  It 
is  well  known  that  contracted  granular  kidney 
is  not  always  evidenced  either  by  the  occurrence 
of  albuminuria  or  of  dropsy.  The  contention  that 
if  organic  renal  failure  existed  the  urea  excretion 
would  probably  be  equally  affected  together  with 
that  of  uric  acid  does  not  hold  good,  if  the  view 
is  adopted  that  uric  acid  is  produced  in  the  kidne3^s, 
while  urea  is  only  eliminated  by  them.  It  is  well 
known  that  in  gouty  subjects  the  kidneys  have 
been  found  at  the  post-mortem  examination  in 
a  diseased  condition,  when  there  have  been  no 
external  manifestations  during  life  of  the  existence 
of  such  renal  mischief.  That  uratic  deposits  are 
frequently  found  in  the  kidneys  of  gouty  subjects 
is  a  matter  of  common  experience,  but  in  the 
absence  of  such  deposits  the  kidneys  may  still 
be  affected.  Sir  Dyce  Duckworth  believes  that 
changes  occur  in  the  kidneys  of  gouty  subjects 
quite   independently   of  uratic    deposits   in   these 


Gour  AND  Plumbism.  59 

organs.  It  has  been  urged  that  the  renal  theory 
is  difficult  to  harmonise  with  the  hereditary 
character  of  gout.  It  is  quite  possible,  however, 
that  there  may  be  in  gouty  subjects  an  hereditary 
tendency  to  the  renal  affection,  since  both  Dr. 
Dickinson  and  Eichorst  have  sliown  that  there 
is  an  hereditary  tendency  to  granular  kidney. 

KIDNEY   DISEASE    AND    GOUT   ALIKE    CAUSED   BY 
CERTAIN   TOXIC    AGENTS. 

Certain  toxic  agents,  which  predispose  to  or 
which  excite  kidney  disease,  are  also  known  to 
produce  gout.  Lead  gives  rise  to  both  chronic 
kidney  disease  and  gout.  In  chronic  lead- poison- 
ing proliferation  of  the  epithelium  of  the  urinary 
tubules  first  occurs,  followed  by  granular  atrophy 
and  excessive  formation  of  interstitial  tissue.  In 
numerous  cases  of  chronic  lead-poisoning  gout 
has  developed.  Very  similar  changes  occur  in 
the  gouty  kidney,  and  it  seems  reasonable  to 
assume  that  the  changes  in  that  organ  in  both 
chronic  lead-poisoning  and  in  gout  so  affect  the 
excreting  apparatus  of  the  kidneys  as  seriously  to 
diminish  their  power  of  eliminating  uric  acid. 
That  lead-poisoning  gives  rise  to  the  accumula- 
tion of  uric  acid  in  the  blood  has  been  shown 
by  Sir  Alfred  Garrod.  Gout  subsequently  de- 
veloped in  two  cases  of  plumbism  in  which  the 
blood  was  found  by  him  to  be  rich,  in  uric  acid. 
He  also  determined  the  excretion  of  uric  acid 
in  the  urine  of  two  patients  to  whom  acetate  of 
lead  had  been  medicinally  administered.     In  both 


6d  The  Pathology  of  Gou'i. 

patients  a  well-marked  diminution  of  uric  acid 
in  the  urine  occurred.  It  was  also  noticed  that 
after  the  lead  had  been  given  for  a  day  or  two,  the 
excretion  of  the  uric  acid  in  the  urine  was  suddenly 
diminished  to  a  very  small  amount — a  condition 
which  usually  lasted  for  a  day  or  two.  This  points 
to  the  fact  that  lead  exercises  a  marked  inhibitory 
effect  on  the  cells  of  the  kidneys  concerned  in 
the  excretion  of  uric  acid.  The  action  of  the 
lead  is  not  due  to  inhibition  of  the  formation  of 
uric  acid,  since  in  cases  of  plumbism  the  blood 
becomes  charged  Avith  uric  acid.  Alcohol  is 
another  body  which  in  excessive  quantities  gives 
rise  to  kidney  mischief,  and  which  may  also  give 
rise  to  gout. 

REASONS    FOR   BELIEF   IN   THE    RENAL   ORIGIN 
OF   GOUT. 

There  is  abundant  evidence  to  show  the 
connection  between  kidney  mischief  and  gout  for 
the  following  reasons  : — (1)  Uric  acid  has,  in  every 
case  in  which  it  has  been  specially  searched  for, 
been  found  in  the  blood  of  cases  of  renal  disease ; 
(2)  uratic  deposits  are  fairly  frequently  found  in 
the  joints  of  persons  who  have  suffered  from  renal 
disease,  but  who  have  never  been  known  to  have 
had  ostensible  gout ;  (3)  kidney  mischief  is  fre- 
quently met  with  at  the  post-mortem  examinations 
of  gouty  subjects ;  and  (4)  certain  toxic  agents 
predispose  to  both  kidney  disease  and  gout. 

The  statement  has  been  made  that  the  absence 
of  ostensible  gout  in  those  cases  of  kidney  disease 


Renal  Origin  of  Gout.  6\ 

in  which   uric   acid   has   been   found   during   Ufe 
in  the   blood,  and  in  which  uratic  deposits  have 
been  found  in  the  joints  after  death,  would  rather 
point  to  the  conclusion  that  something  more  than 
the  presence  of  uric  acid  in  the   blood  and   the 
deposition  of  biurate   in   the  joints   is   necessary 
in  order  to  produce  gout,  and  that  therefore  uric 
acid  may  be  merely  a  by-product  in  that  condition 
of  the  system  called  gout.     This  statement  is  based 
on  an  imperfect  acquaintance   with   the  different 
modes   of  deposition  of  sodium   biurate.     In  my 
opinion,  the  reason  why  deposits  of  sodium  biurate 
are  so  frequently  found  at  post-mortem  examina- 
tions in  the  joints  of  persons  who   have  suffered 
from  granular  kidney  disease,  but  who  have  never 
been  known  to  suffer  from  ostensible  Qrout  durino- 
life,    or    to    complain    of    pain   in   the  joints   in 
which    the    deposits    are    subsequently    found,   is 
that  in  such   cases  the  deposition  of  the  biurate 
into  the  joints  has  been   very   slow  and   gradual 
and  has  never  become  excessive,  whereas  a  some- 
what sudden  and   copious  deposit   is  required  to 
produce  an  attack  of  acute  or  subacute  gout,  and 
a   considerable   amount   must    be   present   in  the 
joints  to  produce  the  deformities  of  chronic  gout. 
Moreover,    the    fact   that   uric   acid    is   found  in 
smaller  proportions  in  the  blood  of  cases  of  granular 
kidney  disease  than  in  cases  of  gout  explains  why, 
in  connection   with  the  former  affection,  the  de- 
position  of  the   biurate  into   the  joints   may   be 
so  slow  and  gradual  as  not  to  produce  the  symp- 
toms of  ostensible  gout. 


62  The  Pathology  of  Gout. 

nature  and  anatomical  seat  of  the  kidney 
affection  causing  gout. 

The  next  question  to  consider  is — What  is 
the  renal  lesion  which,  Ly  interfering  with  the 
proper  excretion  of  uric  acid  by  the  kidneys, 
allows  absorption  of  it  to  take  place  from  those 
organs  into  the  general  circulation,  and  so  starts 
the  gouty  state  ?  In  my  opinion  the  kidney 
affection  may  be  either  a  functional  one  or  an 
organic  one.  My  behef  is  that  a  functional  affec- 
tion of  the  kidneys  always  precedes  any  gouty 
manifestations,  and  that  this  functional  affection 
may  subside,  if  the  exciting  cause  of  it  be  removed, 
or  it  may  pass  on  to  a  structural  lesion.  It  is  the 
HabiUty  to  this  functional  affection  of  the  kidr.eys 
which,  in  my  opinion,  constitutes  the  hereditary 
factor  of  gout.  Such  functional  affection  may, 
however,  be  started  by  various  agents  and  causes, 
among  which  are  excessive  indulgence  in  nitro- 
genous foods,  wines  and  beers,  the  toxic  effect  of 
lead,  and  the  influence  of  nervous  impulses,  such 
as  mental  shocks,  severe  accidents,  etc.  The  ana- 
tomical seat  of  the  presumed  kidney  affection  giving 
rise  to  the  development  of  gout  is  probably  in  the 
epithelium  of  the  convoluted  tubes,  as  that  has 
been  shown  by  Levison"^  to  be  the  primary  seat  of 
disease  in  granular  kidney,  and  by  Oliver  to  be  the 
seat  of  the  kidney  affection  associated  with  lead 
poisoning.  The  increase  of  interstitial  tissue  is 
probably  a  secondary  change. 

*  Zeituchrift  fiir  klininche  Mcdicin,  1894,  xxvi.,  p.  293. 


Gout  and  Kidney  Affections.  63 

If  this  renal  view  be  correct,  it  is  obvious  that 
the  kidney  condition  must  always  be  considered 
in  the  treatment  of  gout,  and  that,  given  diseased 
organs  incapable  of  eliminating  the  normal  amount 
of  uric  acid,  either  some  other  channel  for  its 
elimination  must  be  secured  or  its  formation  must  be 
limited  to  the  diminished  output,  so  that  absorption 
of  it  into  the  general  circulation  may  be  avoided. 
The  retention  of  uric  acid  in  certain  cells  of  the 
kidney,  and  its  subsequent  absorption  into  the 
blood,  is  analogous,  as  Sir  Alfred  Garrod  has  pointed 
out,  to  an  attack  of  jaundice.  When  no  obstruction 
exists  to  the  exit  of  bile  from  the  biliary  passages, 
no  appreciable  amount  of  its  colouring  matter  is 
found  in  the  blood,  but  when  its  free  elimination  is 
checked,  then  absorption  of  it  into  the  blood 
speedily  takes  place. 


64 


CHAPTER  Y. 

Origin  of  uric  acid — Formation  of  uric  acid  from  urea 
in  the  kidneys — Uric  acid  formation  and  liver 
disease — Formation  of  uric  acid  from  nuclein — 
Different  modes  of  formation  of  uric  acid  in  health 
and  in  blood  disorders. 

VIEW   THAT   URIC    ACID   IS    THE    RESULT   OF 
DIMIXISHED   OXIDATION. 

A  COMMONLY  received  notion  as  to  the  origin 
of  uric  acid  is  that  it  results  from  a  less  perfect 
oxidation  of  the  nitrogenous  constituents  of  the 
tissues  than  occurs  when  urea  is  formed.  Ac- 
cording to  this  view  urea  is  the  ultimate  product 
of  the  metabjlism  of  nitrogenised  tissues  in  mam- 
mals, whereas  the  formation  of  uric  acid  is  con- 
sidered as  occupying  an  intermediate  stage  in  the 
metabolism  of  nitrogenised  tissues.  In  birds  and 
serpents  it  has  been  supposed  that  the  nitrogen  is 
eliminated  in  the  form  of  ammonium  quadriurate 
without  having  undergone  the  further  change  into 
urea.  This  notion  is  mainly  based  on  the  observa- 
tion of  the  two  following  facts:  (1)  That  uric  acid 
by  means  of  oxidising  agents  can  be  split  up  into 
urea  and  other  substances ;  (2)  that  in  certain 
reptiles  whose  respiration  is  languid,  and  whose 
temperature  is  low,  the  kidneys  excrete  uric  acid  to 
the  entire  exclusion  of  urea.  The  inference  that 
the   production   of  the  uric  acid  in  such  reptiles 


Diet  and  Uric  Acid.  65 

is  the  result  of  imperfect  oxidation  is,  however, 
disproved  by  the  well-known  fact  that  birds,  whose 
respiration  is  rapid,  and  whose  temperature  is 
higher  than  that  of  mammals,  also,  like  reptiles, 
excrete  uric  acid  to  the  exclusion  of  urea.  80  that, 
although  uric  acid  is  a  less  highly  oxidised  product 
than  urea,  it  is  very  doubtful  whether  it  can  be 
considered  as  an  antecedent  in  the  formation  of  urea 

VIEW   THAT    EXCESS    OF    URIC    ACID    IS    THE    RESULT 
OF   AN   ANIMAL    DIET. 

Another  commonly  received  notion  is  that 
gout  is  accompanied  by  an  excessive  formation 
of  uric  acid,  which  is  usually  attributed  to  the 
ingestion  of  a  too  highly  nitrogenised  diet,  and 
especially  to  an  animal  one.  Virchow,^  however, 
considers  that  a  too  highly  nitrogenised  diet  is 
not  necessarily  the  cause  of  gout,  because  he  has 
often  observed  gout  in  poorlj^-fed  convicts.  Gout 
is  certainly  not  incompatible  with  a  vegetable  diet, 
as,  amongst  certain  birds  kept  in  captivity  and 
living  exclusively  on  grain,  uratic  deposits  have 
been  observed  around  the  joints.  On  the  other 
hand,  animal  food  does  not  necessarily  produce 
uric  acid  in  a  healthy  system,  as  is  shown  by  its 
absence  from  the  urine  of  some  of  the  carnivora. 
It  is  true  that  the  ingestion  of  very  large  quantities 
of  proteid  matter  is  followed  by  an  increased 
production  of  uric  acid,  and,  vice  versa,  but  ap- 
parently it  makes  little,  if  any,  difference  whether 
the   proteid   matter  is   of  animal  or  of  vegetable 

*  Berliner  kUnische  Woche^ischrifl,  1884. 
F 


66  The  Pathology  of  Gout. 

origin.  The  only  reason  that  a  vegetable  diet  is 
less  productive  of  uric  acid  than  an  animal  diet,  is 
in  the  fact  that  the  former  is  poorer  in  proteid 
material,  and  therefore  to  consume  in  the  vegetable 
diet  as  much  proteid  matter  as  is  ordinarily  con- 
sumed in  an  animal  diet  would  require  the  in- 
gestion of  very  large  bulks  of  vegetable  food. 
Therefore  the  assumption  is  not  altogether  correct 
that  the  total  daily  excretion  of  uric  acid  is  greater 
on  an  aniinal  than  on  a  vecfetable  diet.  With  the 
same  intake  of  nitrogen  in  the  two  diets,  there  is 
practically  no  difference  in  the  uric  acid  output. 
This  is  shown  by  the  experiments  of  Bleibtreu,"^ 
who  examined  his  urine  after  three  days'  flesh  diet 
and  after  three  days'  vegetable  diet.  Although 
after  the  flesh  diet  there  Avas  a  considerable  rise  in 
the  amount  of  urea  excreted,  there  was  very  little 
difterence  in  the  uric  acid  excretion.  After  the 
three  days'  flesh  diet  the  uric  acid  excreted  in 
twenty-four  hours  was  0859  gramme,  while  after 
the  three  days'  vegetable  diet  it  was  0-791  grannne. 
Similar  results  were  obtained  by  Hirschfeld,!  who 
found  that  on  a  diet  very  poor  in  nitrogen  he 
excreted  daily  0417  gramme  of  uric  acid;  on  one 
rich  in  albumen  0386  gramme  ;  and  on  a  highly 
albuminous  diet  0*492  gramme. 

That  the  production  of  uric  acid  is  not  depen- 
dent, at  all  events  to  any  great  extent,  on  diet  is 
also  shown  by  the  fact  that  the  same  diet  which  in 
one  class  of  animals  will  produce  uric  acid  will  in 

*  Ffliigers  Archiv,  r>;ind  xlv.,  p.  401. 
f    Virchow's  Archiv,  Band  cxvii.,  p.  301. 


Renal  Excretion.  6; 

another  class  produce  urea.  Thus,  in  the  urine  of 
the  carnivorous  Hon  and  tiger  there  is  a  quantity 
of  urea  and  but  very  Httle  uric  acid  ;  on  the  other 
hand,  the  carnivorous  python  and  boa  excrete  uric 
acid  and  no  urea.  Graminivorous  birds  excrete  uric 
acid  and  no  urea,  whilst  herbivorous  mammals  ex- 
crete quantities  ol  urea  and  but  little  or  no  uric  acid. 
Sir  AVilliam  Roberts,*  comparing  the  functions 
of  the  kidneys  of  birds  and  serpents  with  those  of 
mammals,  considers  that  an  immense  functional 
evolution  has  taken  place  in  the  mammalian 
kidney  ;  that  the  evolution  of  mammalian  urine 
has  probabl}^  turned  mainly  on  the  point  that  the 
mammalian  plan  required  that  the  renal  excretion 
should  be  voided  not  in  the  solid  or  semi-solid 
form,  but  as  a  watery  solution.  This  moditication 
w^ould  require  the  discarding  of  the  sparino-lv 
soluble  uric  acid  as  a  medium  for  the  elimination 
of  nitrogen,  and  the  substitution  ot  a  nitrogenous 
substance  readily  soluble  in  water,  such  as  urea. 
He  considers  it  possible  that  the  reason  why  this 
substitution  has  not  been  completely  effected  is 
that  in  that  particular  the  mammalian  type  has 
not  yet  reached  its  ideal  perfection,  and  that  the 
residuum  of  uric  acid  in  mammalian  urine  may  be 
something  in  the  nature  of  a  vestigial  feature. 

VIEW   THAT   URIC    ACID   IS    FORMED    FROM    UREA 
IX   THE    KIDNEYS. 

In   mammalia,    including    man,'  and   in   birds 
uric   acid   is   absent    from    the    blood    in    health, 

*  Croonian  Lectures  oa  ''  Uric  Acid  Gravel  and  Gout,"  1892. 
p.  33. 


6S  The  Pathology  of  Gour. 

while  urea  is  always  present  in  the  blood.  The 
blood  of  the  renal  artery  is  much  richer  in 
urea  than  the  blood  of  the  renal  vein :  according 
to  Picard  in  the  proportion  of  about  two  to  one, 
according  to  Sir  All  red  Garrod  in  the  proportion 
of  about  three  to  one.  From  his  most  recent 
observations,  Sir  Alfred  Garrod  "^  concludes  that  in 
birds  and  other  uric  acid-excreting  animals  the 
metabolism  of  the  nitrogenised  tissues  is  exactly 
the  same  as  in  mammals.  He  believes  that  urea 
is  the  ultimate  product  of  this  metabolism,  and 
that  the  uric  acid  is  a  subsequent  product  of  the 
union  of  urea  with  some  other  principle  or  prin- 
ciples, glycocine  probably  being  one  of  them.  He 
regards  the  kidney  as  the  organ  whose  function  it 
is  to  manufacture  uric  acid  from  the  nitrogenised 
matters  brought  to  it  in  the  blood,  and  considers  it 
possible  that  the  kidney  contains  different  cells — 
some  lor  the  formation  of  urea,  and  some  for  the 
formation  of  uric  acid — and  that  the  ratio  between 
the  two  may  var}-  in  different  classes  of  animals. 

One  ver}^  strong  argument  against  the  forma- 
tion of  uric  acid  in  the  liver,  spleen,  connective 
tissues,  etc.,  is  that  it  is  never  present  in  the  blood 
ot  mammals  (including  man)  and  of  birds  in  health. 
If  it  were  formed  in  such  organs  or  tissues,  it  must 
be  conveyed  in  the  blood  to  the  kidne3^s.  Since, 
according  to  Sir  Alfred  Garrod's  and  my  o\vn 
investigations,  urea,  and  not  uric  acid,  is  found  in 
the  blood  ot  birds,  and  since  uric  acid,  and  not 
urea,  is  found  in  the  urinary  excrement  of  birds,  it 

*   •' Proceedings  of  the  lioval  Society,"  1893. 


Formation  of  Uric  Acid.  69 

scorns  hi<(lily  probable  that  urea  is  at  least  one  oF 
the  sources  ot  formation  of  uric  acid,  and  that  the 
conversion  of  urea  into  uric  acid  is  effected  in  the 
kidneys.  Dr.  P.  W.  Latham's  ^  explanation  of  the 
formation  of  uric  acid  in  the  animal  economy  is 
that  the  amido-bodies,  glycocine,  taurine,  leucine, 
and  tyrosine,  are  normally  converted  in  the  liver 
into  urea,  but  if  from  any  cause  the  metabolism  of 
glycocine  be  interrupted,  there  w  uld  then  be 
present  in  the  liver  glycocine  and  urea,  which 
would  produce  hydantoic  acid,  and  then  hydantoin, 
and  the  latter,  which  is  freely  soluble,  would  then 
pass  on  in  the  circulation  to  unite  in  the  kidneys 
with  urea  or  with  biuret  to  form  an  ammonium 
salt  ot  uric  acid.  Therefore,  according  to  this  view, 
the  imperfect  metabolism  of  glycocine  is  the  primary 
and  essential  defect  in  connection  with  the  abnormal 
formation  of  uric  acid  in  the  human  system. 

According  to  Dr.  Latham  the  synthesis  of  uric 
acid  from  urea  and  glycocine  takes  place  in  the 
following  steps  : — 

1.  The  urea  and  glycocine  produce  hydantoic 

acid — 

CH4N2O  +  C2H2(NH2)O.OH  =  CgHfiNgOg  +  XH3. 

Urea  Glycocine  Hydantoic  acid 

2.  The  hydantoic  acid  becomes  dehydrated 
and  forms  hydantoin — 

C3HSN2O3  =  CgH.NgOo  +  H^O. 
Hydantoic  acid      Hydantoin 

3.  From  more  of  the  urea  biuret  is  produced — 

2  CHjNaO  =  CJIgNgO^  +  NH3. 

Urea  Biuret 

*  "  Croonian  Lectures,"  1886. 


JO  The  Pathology  of  Gout. 

4.  By  combination  of  hydantoin  and  biuret 
uric  acid  is  produced — 

Hyilantoin  Biuret  Uric  acid 

The  production  of  uric  acid  from  urea  and 
glycocine  may  be  shown  in  a  single  equation  as 
follows — 

3  CH.X.O  +  aH2(NH.,)0.0H  =  C5H4XP3  +  3  NHg  +  2  H.O. 
Urea  Glycocine  Uric  acid 

FACTS   SUPPORTING   THE   VIEW   THAT   URIC   ACID   IS 
FORMED   FROM   UREA    AND   GLYCOCIXE. 

There  are  several  reasons  for  behoving  that  uric 
acid  may  be  formed  from  urea  and  glycocine  in  the 
living  organism.  Horbaczewski  produced  uric  acid 
by  the  interaction  of  urea  and  glycocine,  and  this 
result  was  confirmed  b}^  Dr.  Latham.  Glycocine 
is  certainly  formed  in  the  human  body,  and  prob- 
ably is  one  of  the  antecedents  of  urea,  for  in  man, 
glycocholic  acid,  a  compound  of  glycocine  and 
cholic  acid,  passes  in  the  bile  into  the  intestine, 
and  having  served  its  purpose,  and  its  constituents 
having  been  set  free,  the  glycocine,  together  Avith  the 
other  amido-bodies,  taurine,  leucine,  and  tyrosine, 
pass  in  the  portal  blood  to  the  liver,  and  probably 
in  the  hepatic  cells  are  converted,  or  mainly  con- 
verted, into  urea. 

That  glycocine  is  concerned  in  the  production 
of  uric  acid  is  son^ewhat  probable  from  the  fact 
that  in  the  carnivora,  whose  urine  contains  little 
or  no  uric  acid,  the  bile  contains  no  glycocholic 
but  only  taurocholic  acid,  and  therefore  yields  no 


F0R\TATI0N   OF    UrIC  AcID.  /f 

glycocine.  The  experiments  of  Halin,  Massen, 
Nencki,  and  Pawlow  also  support  the  view  that 
glycocine  is  concerned  in  the  formation  of  uric 
acid.  They  shut  the  livers  of  dogs  almost  com- 
pletely off  from  the  general  circulation  by  diverting 
the  portal  circulation  into  the  inferior  vena  cava, 
and  so  caused  an  increased  amount  of  gl^^cocine  to 
be  sent  ti  the  kidneys,  by  preventing  its  conversion 
into  urea  in  the  liver.  They  found  that,  although 
the  dogs  passed  less  urea  (the  nitrogen  being 
mainly  eliminated  as  ammonium  carbamate),  the 
urid  acid  voided  was  considerably  increased. 
Dr.  Latham"^  believes  that  if  an  excessive  amount 
of  nitroQ^enous  material  is  introduced  into  the 
portal  circulation,  the  portion  which  is  least 
readily  acted  upon  is  the  glycocine,  the  presence  of 
which  promotes  the  formation  of  uric  acid.  He 
considers  that  the  primary  defect  in  gout  consists 
in  the  imperfect  metabolism  of  glycocine.  We 
may  therefore  conclude  that  the  conversion  of  urea 
into  uric  acid  by  the  agency  of  certain  of  the  kidney 
cells  is  at  least  possible,  and  that  this  conversion  is 
effected  by  the  conjugation  of  urea  and  glycocine. 

URIC   ACID    FORMATION   AND   LIVER   DISEASE. 

If  uric  acid  be  formed  in  the  kidneys  from  urea 
and  glycocine  brought  from  the  liver,  it  can  be 
readily  understood  that  alterations  in  the  meta- 
bolism of  the  liver  must  necessarily  affect  the  forma- 
tion and  excretion  of  uric  acid.  This  would  explain 
why  liver  trouble  of  some  kind  or  another   is  so 

"^  Loc.  cit. 


72  The  Pathology  of  Gout. 

commonly  associated  with  gouty  dyspepsia,  and  also 
renders  intelligible  the  fact  that  several  observers 
have  been  unable  to  dissociate  the  connection 
between  liver  troubles  and  gout,  and  have  therefore 
attributed  the  formation  of  uric  acid  to  the  liver. 
For  instance,  Dr.  Murchison  considered  that  gout 
is  a  hereditary  disease  by  virtue  of  the  transmission 
by  parents  to  their  offspring  of  a  defective  power 
of  the  liver,  in  consequence  of  which  its  functions 
are  deranged  with  unusual  facility  ;  as  a  result  of 
this  derangement  of  the  liver  the  metabolism  of  the 
albumen  is  to  a  great  extent  arrested  at  the  stage 
of  uric  acid  formation,  instead  of  going  on  to  the 
final  stage  of  urea  formation.  Dr.  George  Harley 
considered  that  a  strong  relationship  existed  be- 
tween gout  and  hepatic  derangements.  Sir  Dyce 
Duckworth^  is  of  opinion  that  "the  liver  is  the 
organ  in  which  in  health  uric  acid  is  chiefly  formed, 
and  it  is  probably  to  derangement  of  function  in 
this  gland  that  we  must  look  for  over-production 
of  this  substance."  All  these  views  are  rendered 
equally,  if  not  more,  intelligible  by  regarding  the 
liver  as  the  seat  of  production  of  the  antecedents  of 
uric  acid  (urea  and  glycocine),  the  final  conjugation 
of  those  bodies  taking  place  in  the  kidneys. 

VIEW   THAT   URIC    ACID    IS    FORMED    FROM    NUCLEIN. 

Horbaczewski  |  has  shown  that  uric  acid,  as  well 
as  xanthin  and  hypoxanthin,  can  be  prepared  from 

*  "A  Treatise  on  Gout,"  1889. 

t  "  Beitriige  zur  Kentnisse  der  Bildung  der  Harnsiiure  und 
der  Xanthinhason."  Sitzungsb.richt  dor  K.  Acad.  d.  Wiss  in 
Wien.    C,iii.,1891. 


4 


Formation  of  Uric  Acid.  'jI 

spleen  pulp.  The  close  relationship  of  these  three 
bodies  to  one  another  is  shown  by  a  comparison  of 
their  formulae — 

C5H4N4O3         Uric  acid. 
C5H4NP2         Xanthin. 
C5H4NP  Hypoxanthin. 

By  digesting  fresh  spleen  pulp  with  hot  Avater  till 
changes  set  up  by  bacterial  agency  are  started,  he 
found  that  the  fluid,  when  freed  from  albuminous 
bodies,  contained  xanthin  and  hypoxanthin,  but  no 
uric  acid.  By  treating  this  fluid  with  arterial 
blood  and  keeping  the  mixture  at  40°  to  50°  C, 
uric  acid  forms  in  it  after  several  hours.  A  similar 
result  is  produced  by  using  as  the  oxidising  agent 
either  a  dilute  solution  of  hydrogen  peroxide,  or  an 
abundant  supply  of  atmospheric  air.  Horbaczewski 
found  that  the  nitrogen  contained  in  the  uric  acid 
so  formed  was  about  equal  in  amount  to  the 
nitrogen  contained  in  the  xanthin  and  hypoxanthin 
(xanthin  bases).  So  that  there  exist  in  the  spleen 
nitrogenous  substances  which  can  be  transformed, 
at  all  events  in  part,  into  xanthin  bases  or  into  uric 
acid.  The  xanthin  bases  when  once  formed  cannot 
be  further  oxidised  into  uric  acid.  Horbaczewski 
brings  forward  proof  that  the  substance  which 
yields  xanthin  bases  and  uric  acid  is  the  nuclein  ot 
the  spleen  cells.  It  was  found  that  when  pure 
j-|j-|p1pi|-i^  prepared  from  spleen  pulp,  was  dissolved 
in  very  weak  alkali,  and  digested  with  blood  at 
40°  C,  uric  acid  was  formed.  Sadowenj  and  For- 
manck  have  shown  that  uric  acid  can  be  prepared 
in  a  similar  manner  from  almost  all  the  tissues  and 


74  The  Pathology  of  Gout. 

organs  of  the  body,  and  conclude  that  the  nuclein 
contained  in  the  cells  is  the  mother-substance. 

It  havinsT  thus  been  shown  that  uric  acid  could 
be  prepared  from  nuclein  outside  the  system, 
an  attempt  was  next  made  to  ascertain  Avhether 
a  similar  decomposition  could  also  occur  in  living- 
human  beings.  Horbaczewski  found  that  the 
excretion  of  uric  acid  c?.n  be  increased  either  by 
the  administration  of  nuclein  with  food,  or  by 
the  subcutaneous  injection  of  a  solution  of  it. 
Umber  ^  found  that  the  administration  of  a  large 
amount  (500  grammes  per  diem)  of  food  like 
thymus,  wdiich  contains  a  considerable  quantity 
of  nuclein,  increases  the  excretion  of  uric  acid 
as  compared  with  its  excretion  when  a  similar 
amount  of  flesh  is  given.  The  same  amount  of 
liver  given  to  one  person  caused  an  effect  similar 
to  that  caused  by  thymus,  but  in  others  its  action 
was  less  marked.  Kidney  and  brain  administered 
as  food  yielded  nearly  the  same  amount  of  uric 
acid  as  flesh. 

From  his  experiments  Horbaczewski  concludes 

that  uric  acid   is   formed   in   health   by   the  dis- 

I  integration  of  nuclein,  and  that  sudden  variations 

in  uric  acid  production  may  be  due  to  the  breaking 

up  of  leucocytes  and  conversion  of  their  nuclein 

into  uric  acid  or  xanthin  bases  Avithin  the  system. 

It  has    been   shown   b}^  many   observers   that   a 

^        temporary    or  permanent    lourocytosis   is    always 

^        accompanied   by_an   increased   excretion   of  uric^ 

np.ifl       A    relationship    between   the    number    of 

*  Zcilschnft  fiir  Idinische  Mcdicin,  1896,  xxix.,  pp.  174-189. 


Formation  of  Uric  Acid.  75 

leucocytes  in  the  blood  and  the  excretion  of  uric  ) 
acid  is  observable  in  human  beings  during  fasting 
and  after  taking  food.  During  fasting  the  number 
of  leucocytes  diminishes,  and  the  amount  of  uric 
acid  excreted  falls ;  after  taking  food  the  number 
of  leucocytes  increases,  and  the  amount  of  uric 
acid  excreted  rises.  The  increase  in  the  number 
of  leucocytes  in  the  blood  after  a  meal  appears 
to  be  due,  at  all  events  in  part,  according  to 
Hofmeister,  ^  to  the  rapid  increase  of  lymph  cells 
in  the  adenoid  tissue  of  the  stomach  and  intestines 


^uring  digestion,  whence  they  are  discharged 
into  the  lymph  stream,  and  linally  into  the  blood. 
Gamprecht  f — ^^'ho  uses  the  term  "  alloxur  bodies  " 
in  Kossel  and  Krliger's  sense  as  meaning  those 
bodies  which  have  an  alloxan  and  urea  nucleus, 
and  therefore  as  including,  besides  uric  acid, 
xanthin,  guanin,  hypoxanthin,  adenin,  and  their 
derivatives — found  that  in  the  exceptional  cases 
of  leucocythsemia  in  which  the  uric  acid  excretion 
is  normal  or  diminished,  the  alloxur  bases  are 
increased,  and  that  their  amount  varies  directly 
with  the  amount  of  leucocytosis.  He  gives  one 
case  of  his  own  in  which  this  is  shown  very 
clearly,  and  points  out  that  it  forms  an  additional 
support  to  Horbaczewski's  view  that  uric  acid 
comes  from  degeneration  of  leucocytes,  and  is 
formed  from  their  nuclein. 

From   a   consideration    of  all   the    work   that 

*  Arch IV  fur  Exper.  Fathologie  und  PharniaJcolorjie,  Band,  xxii., 
p.  306. 

•j-  Centralblatt  far  allgemcwe  Fathologie  iind  pathologischea 
Anatomic,  1896,  vol.  vii.,  p.  820. 


yG  The  Pathology  of  Gout. 

has  been  done  in  connection  with  leucocytosis  and 
the  excretion  of  uric  acid,  it  is  clear  that  there 
is  no  constant  ratio  between  the  number  of 
leucocytes  and  the  amount  of  uric  acid  excreted, 
for  there  may  be  leucocytosis  without  increase 
of  uric  acid,  as  there  may  be  an  increase  of  uric 
acid  without  leucocytosis.  I  think  that  in  cases 
of  leucocythcemia,  severe  anaemia,  etc.,  where  uric 
acid  is  present  in  the  blood,  it  is  probably  derived 
from  the  nuclein  of  leucocj'tes  or  other  cells.  It 
is,  however,  in  my  opinion,  wrong  to  draw  the 
further  inference  that  the  source  of  the  uric  acjj 


ftxfvrpitftfl  in  "healthy  is"  the  nuclein  derived 
leucocytes  thrpnghout  the  bodY.  If  such  were 
the  case,  uric  acid  would  be  found  in  the  blood 
in  health ;  but,  as  previously  shown,  it  is  not. 
Moreover,  in  birds  there  is  no  special  leucocytosis 
to  account  for  the  lara^e  formation  and  excretion 
of  uric  acid  that  occurs. 

In  connection  with  leucocj^thremia,  an?emia, 
etc.,  the  excretion  of  uric  acid  in  the  urine  may 
rise  to  six  times  the  normal  amount,  and  yet  no 
signs  of  gout  appear.  The  reason  for  this  non- 
development  of  the  symptoms  of  gout  in  connec- 
tion Avith  these  diseases  is  that  ilie  kidneys  remain 
in  a  sound  condition,  and  therefore  the  uric  acid 
(which  in  these  diseases  is  "prohcdjly  derived,  from 
nuclein)  is  readily  and.  rapidly  excreted  by 
them.  This  knowledge  of  the  derivation  of  uric 
acid  from  nuclein  in  connection  with  diseases 
associated  with  leucocytosis  has,  in  my  opinion, 
proved   a   stumbling-block   to  many    writers   and 


Diet  and  Uric  Acid.  77 

observers  in  their  conception  of  the  pathogenesis 
oF  gout.  For  it  by  no  means  follows  that  because 
in  diseases  associated  with  leucocytosis  the  uric 
acid  which  appears  in  the  blood  is  derived  from 
nuclein,  therefore  such  must  be  its  source  in 
gout.  The  simple  fact  is  that  gout  is  not  a 
disease  associated  with  leucocytosis,  and  therefore 
the  uric  acid  of  s^out  cannot  be  derived  from 
nuclein. 

VIEW   THAT   PART   OF   THE    URIC    ACID    IS    INTRO- 
DUCED   READY-FORMED   IX    FOOD. 

Dr.  Haig,  who  in  my  opinion  wrongly  ascribes 
to  uric  acid  an  almost  universal  role  in  the  causa- 
tion of  disease,  claims  that  the  uric  acid  excreted 
in  the  urine  comes  from  two  sources: — (1)  The 
uric  acid  which  is  formed  in  the  body  out  of 
nitrogenous  food ;  (2)  the  uric  acid  introduced  into 
the  body  ready-formed  in  certain  articles  of  diet, 
such  as  meat,  meat  extracts,  soup,  tea,  coffee,  etc. 
He  consideis  that  fiesli  diet  increases  both  the 
introduction  and  the  formation  of  uric  acid,  a  view 
which  is  opposed  to  the  previously  quoted  ex- 
perimental results  obtained  by  Bleibtreu  and  by 
Hirschfeld.  Dr.  Haig  ^  gives  the  quantities  of  uric 
acid  which  a  man  may  introduce  into  his  system 
with  an  ordinary  dinner  as  follows  : — 

grain. 
8  oz.  soup  .  .  containing  0"0'2  per  cent,  uric  acid  =  U'TO 
•2  oz.  fish  .         .  „.  003         ,,  ,,        =  0-26 

3  oz.  meat        .         .  „  O-Oi         „  ,,        =:  0-52 

\  drachm  meat  extract  „  0-80         ,,  „        .—  0-24 

1-72 
*  Brit.  Med.  Journ.,  189-i,  ii.,  p.  1299. 


yS  The  Pathology  of  Gout. 

As  far  as  I  can  ascertain  from  Dr.  Haig's 
writings,  he  has  never  identified  b}^  the  nuirexide 
test  this  uric  acid  reported  to  be  present  in  these 
various  articles  of  diet.  These  estimations  depend 
solely  on  the  application  of  Haycraft's  process 
to  the  articles  of  diet,  and  the  subsequent  calcula- 
tion of  the  silver  precipitate  so  obtained  in  terms 
of  uric  acid.  Recently  Dr.  Haig  has  shown  a 
tendency  to  shift  the  responsibility  from  uric 
acid  to  xanthin,  and  therefore  refers  to  the  amounts 
of  uric  acid  or  xanthin  which  he  states  are  present 
in  various  foods.  This  assumption,  that  the  sub- 
stance stated  to  be  present  in  foods,  if  not  mic 
acid,  is  xanthin,  is  however  untenable,  since 
xanthin  is  not  estimated  by  Haycraft's  process. 
That  Dr.  Haig's  view  as  to  the  direct  introduction 
of  uric  acid  in  articles  of  diet  is  an  erroneous  one 
is  shown  by  the  absence  of  uric  acid  from  the 
blood  of  man  and  animals  in  health. 

RATIO    OF   URIC   ACID   ELIMINATION   TO   THAT   OF 

UREA. 

Dr.  Haig  has  also  advanced  the  theory 
that  normally  there  is  a  constant  ratio  of  1  to  85 
between  the  uric  acid  and  urea  formation,  and 
that  if  the  uric  acid  excretion  falls  below  this 
ratio  it  is  due  to  the  retention  and  storage  of 
uric  acid  in  the  liver,  .spleen,  kidneys,  joints,  and 
fibrous  tissues,  whereas  an  increase  in  the  pro- 
portion of  uric  acid  to  urea  is  due  to  the  washing 
out  from  its  storage  places  of  the  deposited  uric 
acid.      According   to   this    view,    the    amount   of 


Uric  Acid  and  Urea.  79 

uric   acid  produced   in   relation   to   urea   in   each 
individual  is  a  constant  factor,  the   variations  in 
the   amounts   eliminated   being   due   on    the   one 
hand  to  excessive  storage,  and  on  the  other  to  the 
discharge  of  the   stored-up  supply.     This  theory 
of  the  existence  of  a   normal   ratio   of  uric   acid 
to  urea,  and  of  every  departure  from  it  being  due 
to  a  pathological  cause,  is  disproved  by  the  follow- 
ing   experiments: — (1)    Bleibtreu    and    Schultze,^ 
experimenting    on    themselves,   showed   that    the 
ratio   between   uric    acid   and   urea   can   be   con- 
siderably altered  by   means  of  the   diet   without 
the    general    health    being    influenced.      (2)    Dr. 
Herringham   and   Mr.  Groves,!   as    the  result   of 
a  series  of  experiments  that  they  made,  entirely 
fail  to   corroborate   Dr.    Haig's   observations,   and 
think  that  either  what  was  true  for  his  system  was 
not  true  for  theirs,  or  that  Dr.  Haig's  results  were, 
to   quote   their   own  words,    "  inaccurate  and  de- 
ceptive   owing    to   his   having   employed   a    very 
uncertain  and  inaccurate  method  for  the  estimation 
of  uric   acid."     (3)    The   following  results   of  the 
determinations  which  I  have  made  of  the  total  daity 
eliminations  of  uric  acid   and   urea   in   the  urine 
of  a   healthy   adult    man,   and   which   consist   of 
observations  extending  over  a  period  of  fifty  days, 
show  that  the  ratio  of  uric  acid  to  urea  varied  from 
1  :  28  to  1  :  55  (the  average  being  1  :  42),  although 
throughout   the   entire   period  the   individual  re- 
mained in  good  health. 

*  FjVdger's  Archiv,  Band  xlv.,  p.  401. 
■f  Journal  of  F/i//siolor/i/,  1891. 


TABLE   III. 

Fifty  daily  eliminations  of  uric  acid  and  urea  of  a  healthy  adult  man 

on  a  mixed  diet. 


No.  of  oz.  of 

Uric  acid  excreted 

Urea  excreted  per 

Ratio  of  uric  acid 

urine  per  diem. 

per  diem  (gram  me). 

diem  (grammes). 

to  urea. 

C3 

0-65i 

28-34 

1:43 

68 

0-714 

31-62 

44 

72 

0-626 

29-82 

47 

42 

0-532 

29-39 

55 

61 

0-819 

30-19 

37 

56 

0  663 

25-22 

38 

65 

0-616 

27-67 

45 

59 

0-612 

24-44 

40 

41 

0-826 

30-32 

11 

57 

0-705 

21-91 

31 

49 

0  618 

31-27 

50 

•    63 

0-751 

27-57 

37 

43 

0-722 

28-89 

40 

61 

0-569 

23-44 

41 

51 

0-652. 

29-89 

46 

6) 

0-608 

2700 

44 

56 

0-591 

27-71 

47 

50 

0-561 

27-54 

49 

6C 

0-630 

27-91 

44 

45 

07*2 

26-56 

36 

45 

0-550 

23-60 

40 

60 

0-640 

31-34 

49 

61 

0-581 

28-34 

49 

61 

0-537 

22  35 

41 

64 

0-572 

26-49 

46 

53 

0-595 

21-24 

36 

55 

0-7G4 

24-73 

:32 

69 

0-637 

28-58 

45 

63 

0-526 

23-13 

:44 

72 

0-583 

28-88 

.49 

45 

0-620 

24-26 

:39 

45 

0-698 

28-01 

:40 

52 

0-680 

3004 

:44 

69 

0-705 

33-16 

:47 

40 

0-837 

25-62 

:31 

42 

0-728 

30-54 

:42 

67 

0-605 

30-11 

:45 

44 

0-550 

29-50 

:53 

54 

0-554 

29-88 

:54 

62 

0-582 

26-13 

:45 

55 

0-515, 

22-15 

:43 

55 

0  632 

27-14 

:43 

54 

0-585 

28-34 

:48 

66 

0776 

28-05 

:36 

49 

0-536 

25-20 

:47 

67 

0-560 

23-56 

:42 

45 

0-550 

21-63 

:39 

35 

0-660 

23-10 

:35 

55 

0-624 

23-09 

:37 

87 

0-691 

19-76 

1.28 

Uric  Acid  and  Urea. 


8i 


TABLE  IV. 


Excretion  of 

Exci'etiou  of 

Eatio  of  uric 

uric  acid. 

urea. 

acid  to  urea. 

Paily      average      in 

gTanimes  ... 

0-639 

26-89 

1  :42 

Daily     average      in 

grains 

9-8 

41o0 

1:42 

Average  in  24  hours 

for  each  lb.  of  bodv 

weight  (in  grains) 

•07 

3-19 

It  is  evident  from  the  above  results  that  no 
constant  ratio  exists  in  a  given  individual  between 
the  excretion  of  uric  acid  and  urea.  Variations 
in  the  daily  elimination  of  uric  acid  in  healthy 
individuals  are  not  due  to  the  sweeping  out  of 
uric  acid  from  the  different  organs  and  tissues 
into  the  blood,  for  uric  acid  is  never  found  in 
the  blood  of  healthy  persons.  Differences  from 
day  to  clay  in  the  uric  acid  excretion  probably 
depend  upon  the  amount  of  glycocine  leaving  the 
liver  and  passing  on  to  the  kidn-eys ;  this  factor 
vv^ould  be  affected  by  variations  in  the  metabolism 
of  the  liver,  which  may  be  induced  by  changes 
in  the  quality  or  quantity  of  the  diet,  by  the 
amount  of  exercise,  and  by  various  nervous  in- 
fluences. Dr.  Latham  ^  has  suggested  a  possible 
reason  why  those  persons  wdio  have  a  tendency  to 
gout  and  who  take  little  exercise  tend  to  develop 
the  disease.  It  is  that  insufficient  muscular 
exercise  tends  to  the  formation  of  glj^cocine.  This 
is  seen  in  the  case  of  horses  which  wdien  put  to 
hard    w^ork  eliminate   benzoic  acid   in   the   urine, 

*   "  On  the  Formation  of  Uric  AciJ  in  Animals,"  1884,  p.  42. 


Sz  The  Pathology  of  Gout. 

but  if  kept  in  the  stable  for  some  time  benzoic 
acid  appears  in  the  urine  in  combination  with 
glycocine  as  hippuric  acid,  which  is  benzoyl- 
glycocine. 

DIFFERENT   MODES   OF    FORMATION   OF   URIC   ACID 
IX    HEALTH    AND    IN    BLOOD   DISORDERS. 

From  a  consideration  of  the  various  views  as  to 
the  origin  of  uric  acid,  I  think  it  is  evident  that 
there  are  two  distinct  and  different  ways  in  which 
uric  acid  may  originate.  (1)  In  health  I  believe  that 
it  is  only  formed  in  the  kidneys,  probably  from  urea 
and  glycocine,  and  that  it  is  at  once  eliminated 
in  the  urine.  If,  fr  mi  any  functional  or  organic 
affection  of  the  uric  acid-eliminating  cells  of  the 
kidneys,  its  proper  excretion  is  inhibited,  then 
it  is  absorbed  into  the  general  circulation  and 
constitutes  the  store  from  which  the  uratic  de- 
posits of  gout  are  formed.  (2)  In  diseases  which 
are  accompanied  by  leucocytosis  I  believe  that 
uric  acid  may  be  formed  from  the  nuclein  of 
leucocytes  in  the  spleen  and  possibly  throughout 
the  system  generally,  but  that  such  uric  acid  is 
readily  eliminated  by  the  kidneys,  which  remain 
sound  as  regards  their  uric  acid-secreting  struc- 
tures ;  consequently  gouty  deposits  never  occur  in 
connection  with  such  diseases.  The  two  different 
modes  of  formation  of  uric  acid  might  be  dis- 
tinguished as  the  urea  formation  and  tie  nuclein 
formation  of  uric  acid. 


83 


CHAPTER    YI. 

Composition  of  the  amorjjhous  urate  deposit  of  urine — ■ 
Causes  of  uratic  deposition — Formation  of  tJie  gouty 
dejjosit — Time  occupied  in  the  conversion  of  sodium 
quadriurate  into  hiurate — Seats  of  uratic  deposition 
in  gout. 

As  I  take  the  view  tliat  the  uratic  deposits  of 
o'out  are  derived  from  uric  acid  absorbed  into  the 

o 

blood  from  the  kidneys,  it  will  be  advisable  to 
consider  next  the  various  causes  for  its  crystal- 
lisation in  the  form  of  sodium  biurate  from  the 
blood,  and  the  reasons  wdiy  the  biurate  selects 
certain  tissues  as  seats  for  its  deposition.  It  is 
necessar}^  briefly  to  consider  (a)  the  form  in  which 
uric  acid  is  absorbed  into  and  circulates  in  the 
blood  :  (/>)  the  form  in  which  it  is  deposited  from 
the  blood  or  fluids  of  the  body. 

FORM    IX   WHICH   URIC    ACID    EXISTS   IN   THE 
CIRCULATIOX. 

Sir  AYilliam  Roberts  ^  has  shown  that  the 
amorphous  urate  deposit  of  human  urine  is  of 
the  same  composition  as  the  solid  or  semi-solid 
urinary  excrement  of  birds  and  serpents,  the  only 
difference  being  one  of  physical  form.  The  deposit 
from  human  urine  is  amorphous,  whilst  the  urinary 
excrement  of  birds  and  serpents  consists  ot  minute 
crystalline   spheres.      Sir    William   Eoberts  shows 

*  Crooniiii  Lectures  on  "  Uric  Acid  Gravel  and  Gout,"  1892. 


84  The  Pathology  of  Gout. 

that  this  clifterence  in  physical  form  is  a  mere 
accident  of  molecular  aggregation,  since,  under 
certain  conditions,  the  amorphous  urate  deposit 
can  be  transformed  into  crystaUine  spheres,  whilst 
the  crystalline  urinary  substance  of  birds  and 
serpents  can  be  converted  into  amorphous  deposit. 
Dr.  Bence  Jones  ^  was  the  first  to  show  that  the 
amorphous  urate  deposit  yielded  to  water,  a  soluble 
moiety  consisting  of  true  biurate,  and  left  a  sedi- 
ment consisting  of  pure  uric  acid,  and  from  the 
results  of  his  analj^'ses  he  inferred  that  the 
amorphous  urate  deposit  consisted  of,  or  at  least 
often  contained,  a  molecule  of  biurate  in  loose 
combination  with  a  further  molecule  of  uric  acid. 
Sir  William  Roberts  took  up  and  continued  the 
investigation  dropped  by  Dr.  Bence  Jones  thirty 
vears  before,  and  has  conclusivelv  shown  that 
a  third  order  of  uric  acid  salts — the  quadriurates — 
exists,  and  that  the  amorphous  urate  deposit  of 
human  urine  and  the  urinar}^  excretion  of  birds 
and  serpents  belong  to  this  order,  and  consist 
of  a  true  and  definite  compound  of  biurate  and 
uric  acid  in  the  proportion  of  one  molecule  of 
each.  Sir  William  Roberts  concludes  that  the 
quadriurates  are  the  physiological  combinations  of 
lU'ic  acid.  They  exist  normally  in  the  urine,  and 
constitute  the  only  form  in  which  uric  acid  exists 
in  normal  urine.  All  the  morbid  phenomena  due 
to  uric  acid  probably  arise  from  secondary  changes 
in  the  quadriurates.  The  amorphous  urate  or 
quadriurate  dej^osit  of  urine  is  generally  referred 

*  Journal  of  the  Chemical  Society,  1862,  vol.  xv.,  p.  201. 


-     Amorphous  Urate  Deposit.  85 

to  as  consisting  of  a  mixture  of  the  potassium, 
sodium,  ammonium,  and  calcium  urates.  As  far 
as  I  can  ascertain,  however,  no  quantitative  deter- 
mination of  the  bases  in  the  deposit  has  yet  been 
made.  The  nearest  approach  to  it  is  an  analysis 
made  b}^  Sir  WiUiam  Roberts  ^  of  a  sample  of 
amorphous  urate  deposit  prepared  by  an  artificial 
process  with  potassium  carbonate,  which  would 
therefore  most  probably  contain  more  potassium 
than  the  natural  deposit.  I  therefore  considered 
it  advisable  to  determine  the  actual  bases  present 
in  the  amorphous  urate  deposit  and  their  relative 
proportions, 

COMPOSITION   OF   THE    AMORPHOUS   URATE   DEPOSIT 

OF   URINE. 

The  deposit  was  obtained  from  several 
gallons  of  acid  urine  passed  by  patients  suffering 
from  febrile  diseases,  and  was  collected  on  a  filter 
and  allowed  to  drain.  It  was  decomposed  by 
boiling  with  distilled  water  and  excess  of  hydro- 
chloric acid,  the  mixture  was  then  allowed  to  cool, 
filtered  from  the  deposited  uric  acid,  and  the  fil- 
trate,-which,  then  contained  the  bases  in  the  form 
of  chlorides,  was  evaporated  to  dryness.  The 
residue  was  taken  up  with  distilled  water,  filtered 
from  th.e  minute  amount  of  uric  acid  left  in 
solution  after  precipitation  of  the  bulk  of  the  acid, 
and  evaporated  to  dryness.  Part  of  the  residue 
was  submitted  to  qualitative  analysis,  and  found  to 

*  Croonian  Lectures  on  "  Uric  Acid  Gravel  and  Gout,"  1892, 
p.  20. 


86  The  Pathology  of  Gout. 

contain  ammonium,  sodium,  and  potassium,  with 
vei'}'  small  traces  of  calcium  and  magnesium.  The 
amounts  of  ammonium,  sodium,  and  potassium 
Avere  then  estimated  in  the  usual  manner  in  the 
other  portion,  when  their  relative  quantities  were 
found  to  be  as  follows  : — 

Parts  per  100. 
Ammonium      ...  ...  ...  ...         46 

Sodium...  ...  ...  ...  ...         40 

Potassium         ...  ...  ...  ...         14 

These  amounts,  calculated  as  the  respective 
quadriurates,  would  approximately  give  the  follow- 
ing composition  for  the  amorphous  uratic  deposit 
that  naturally  forms  in  acid  febrile  urines  : — 

7  molecules NH4HC5HJN4O3, H^,CgH2X403- Ammonium  quadriiu-ate. 

0  molecules  XaHCgH^X^Og,  HoC^HoX^Oo— Sodium  quadriurate. 

1  molecule  KHC^H^N^Oo,  H^CgH.jX403 — Potassium  quadi-iurate. 

The  uric  acid  which  is  formed  in  the  kidneys  is 
probably  at  once  converted  into  the  mixture  of 
these  three  quadriurates,  which  in  the  normal 
state  are  then  excreted  dissolved  in  the  urine.  If, 
hoAvever,  any  absorption  of  them  takes  place  into 
the  blood,  as  probably  occurs  in  the  gouty  state, 
the  ammonium  and  potassium  quadriurates  would 
be  converted  by  the  sodium  carbonate  of  the  blood 
into  sodium  quadriurate,  which  would  constitute 
the  sole  compound  of  uric  acid  at  first  circulating 
in  the  blood.  It  is  from  this  bod}'  that  the  sodium 
biurate,  of  which  the  gout}^  deposits  consist,  is 
derived 

FORMA.TIOX   OF   THE    GOUTY   DEPOSIT. 

Sir  William  Eoberts  investigated  the  behaviour 
of  free  uric  acid  with  blood  serum  and  kindred 


Artificial  Blood  Serum,  87 

media,  Avith  tlio  objecfc  of  endeavouring  to  tln-ow 
light  on  the  mode  in  which  sodium  binrate 
originates  in  the  body,  and  on  the  conditions  which 
control  the  precipitation  of  sodium  biurate  in  the 
gouty  system.  He  experimented  with  sohitions 
of  uric  acid  in  blood  serum  and  in  a  standard 
solvent  which  was  prepared  as  follows : — 

CompoHition  of  Itohcrts's  standard  f'Olvcnt — • 

Socliiim  chloride  ...  ...  ...     O'o  gramme. 

Sodium  bicarbonate    ...  ...  ...     0'2  gramme. 

Distilled  water...         ...         ...          ...     100  c.c. 

This  solution  represents  the  blood  serum,  in  so 
far  as  its  saline  ingredients  arc  concerned.  Sir 
William  Roberts  found  that  it  reacted  with  uric 
acid  and  the  urates  in  the  same  manner  as  blood 
serum  itself,  and  in  the  same  manner  as  a  solution 
comprising  all  the  salts  of  the  serum  in  their 
proper  proportions.  He  found  that  blood  serum 
and  the  standard  at  the  temperature  of  the  human 
body  both  dissolved  uric  acid  to  the  extent  of 
about  one  part  in  500,  thus  exhibiting  about  twenty 
times  the  solvent  power  that  the  same  media  exer- 
cise on  sodium  biurate.  The  chemical  and  solvent 
power  is  dependent  on  the  sodium  carbonate 
contained  in  them,  and  is  due  to  that  body  con- 
verting the  uric  acid  into  sodium  quadriurate. 
This  sodium  quadriurate  which  remains  in  solution 
is  gradually  converted  by  the  excess  of  sodium 
carbonate  into  sodium  biurate,  and  this,  on  account 
of  its  lessor  solubility  is  eventually  precipitated  in 
the  crystalline  form.  Sir  William  Roberts  infers 
from  these  results  that,  in  the  normal  state,  uric 
acid  is  primarily  taken  up  in  the  systein  as  quadri- 


S8  The  Pathology  of  Gout. 

urate,  and  that,  as  such,  it  circulates  in  the  blood. 
The  detained  quadriurate,  circulating  in  a  medium 
rich  in  sodium  carbonate,  is  gTadually  transformed 
by  the  latter  into  sodium  biurate,  which  is  less 
soluble  and  is  probably  less  easily  excreted  by  the 
kidneys  than  the  quadriurate.  This  biurate  is  prob- 
abl}^  not  precipitated  at  once,  since  it  vrould  most 
probablj^  pass  at  first  into  the  hydrated  or  gela- 
tinous condition  which  is  a  much  more  soluble 
modification  of  sodium  biurate  than  the  crystalline 
form  ;  but  wiih  due  laj^se  of  time,  and  increasing 
accumulation,  it  passes  into  the  anhydrous  or 
crystalline  condition,  and,  as  this  form  is  almost 
insoluble,  precipitation  of  it  occurs,  or  is  likely 
to  occur. 

The  reason  that  in  leucocyth^mia  and  other 
blood  diseases  no  uratic  deposits  occur  is  that  the 
uric  acid  produced  in  the  various  organs  or  tissues  is 
discharged  into  the  blood  as  a  quadriurate,  and,  as 
this  requires  some  hours  for  its  maturation  before  it 
is  possible  for  it  to  deposit  sodium  biurate,  there  is 
abundant  time  for  the  kidneys  to  eliminate  it,  pro- 
vided these  organs  are  sound.  In  connection  with 
gout,  if  the  view  is  correct  that  defective  elimina- 
tion of  uric  acid  by  the  kidneys  always  occurs,  the 
conditions  are  quite  different.  In  gout  uric  acid  is 
absorbed  from  the  kidneys  into  the  general  cir- 
culation owing  to  the  partial  failure  of  the  uric  acid- 
excreting  function  of  the  kidneys.  The  uric  acid 
is  absorbed  as  the  sodium  quadriurate,  Avhich,  dis- 
solved in  the  blood,  gradually  passes  through  the 
maturation   process    and    forms    sodium    biurate. 


Deposition  of  Sodium  Biurate.         89 

~When  the  amount  of  the  biurate  in  the  blood  is 
more  than  that  fluid,  can  retain  in  solution,  then 
deposits  of  it  occur  in  those  tissues  which,  either 
on  account  of  having  received  previous  slight 
injuries  or  because  of  their  poor  v-ascular  supply, 
specially  favour  its  deposition. 

TIME    OCCUPIED   IN    THE    CONVERSION    OF   THE 
QUADRIURATE    INTO    THE   BIURATE. 

The  period  of  time  required  for  the  conver- 
sion of  the  sodium  quadriurate  contained  in  the 
blood  into  the  biurate  is  variable,  and  is  doubtless 
dependent  on  several  factors,  such  as  the  amount 
of  quadriurate  present,  and  the  proportions  ot 
various  saline  constituents  of  the  blood,  which 
may  either  hasten  or  inhibit  the  change.  This 
last-mentioned  group  of  factors  is  a  most  import- 
ant one  in  connection  with  the  therapeutical 
treatment  of  gout.  From  an  experimental  in- 
quiry into  the  subject  that  I  have  made,  I  find 
that  when  the  blood  serum  is  saturated  with 
sodium  quadriurate  and  kept  at  the  body  tem- 
perature, deposition  of  sodium  biurate  does  not 
commence  till  the  end  of  t^vo  hours,  and  is  not 
complete  till  many  hours — sometimes  days — have 
elapsed.  Probably  in  no  pathological  condition  is 
there  so  much  sodium  quadriurate  present  in  the 
blood  as  to  produce  saturation.  The  smaller  the 
proportion  of  quadriurate  present,  the  longer  is 
the  deposition  of  sodium  biurate  delayed,  and 
the  longer  is  the  time  required  to  complete  its 
precipitation. 


90  The  Pathology  of  Gout. 

seats  of  u;uvtic  deposits  in"  gout. 

Uratic  deposits  are  found  almost  exclusively  in 
structures  belons^ino^  to  the  connective-tissue  class — 
in  cartilages,  ligaments,  tendons,  and  in  the  cutane- 
ous and  subcutaneous  connective  tissue.  They  are 
conspicuously  absent  from  the  muscular  tissue,  and 
from  the  substance  of  the  liver,  spleen,  brain,  and 
lungs.  Uratic  deposits  have  been  very  occasionally 
found  in  the  following  places  : — In  the  mitral  and 
aortic  cardiac  valves,  in  atheromatous  patches  in  the 
aorta,  in  the  walls  of  veins,  in  the  crico-arytenoid 
Hofaments,  in  the  vocal  cords,  in  the  Avails  of 
bronchial  tubes,  in  the  mucous  follicles  of  the 
pharynx,  upon  the  meninges  of  the  brain  and 
spinal  cord,  upon  the  spinal  nerve  sheaths,  in  the 
sclerotic  coat  of  the  eye,  and  the  fibrous  envelope 
of  the  retina.  It  is  always  in  the  fibrous  tissue 
which  participates  in  the  formation  of  the  nervous 
envelopes,  that  the  deposit  is  found.  Uratic 
crystals  have  also  on  two  occasions  been  detected 
in  the  sputa  of  gouty  patients.  Sir  William  Roberts 
considers  that  the  visceral  neuroses  and  the 
thrombosis  and  embolism  mot  with  in  gout  are  not 
the  result  of  the  dissolved  uric  acid  in  the  blood, 
but  are  duo  to  precipitation  of  minute  crystals  of 
sodium  biurate  either  in  the  substance  of  the  organs 
or  in  the  blood  itself. 

ANATOMICAL   SEAT   OF    THE    DEPOSIT  IN    CARTILAGES. 

The  uratic  deposit  first  occurs  in  the  central  por- 
tion of  articular  cartilage — a  point  farthest  from 
the  network  of  nutrient   capillaries   and   a   point 


Urat/c  Deposits  av  Cartilage.  91 

whose  nutrition  is  more  easily  retarded.  It.  is  also 
probably  the  point  of  greatest  pressure,  hence  a 
long  walk,  a  dance,  or  similar  violent  exercise  may 
precipitate  an  attack  of  gout.  Uratic  deposits 
occur  in  cartilages,  ligaments,  synovial  membranes 
and  their  fringe-like  processes.  In  synovial  mem- 
branes the  deposit  is  not  on  the  surface,  but 
in  the  subserous  tissue.  Ebsteui  *  states  that 
directly  under  the  surface  of  the  cartilage  a  very 
shallow  tissue  layer  exists  in  which  crystals  are 
wanting,  and  in  the  layer  immediately  beneath  this 
the  crystals  are  most  plentiful.  He  agrees  with  Sir 
Alfred  Garrod  that  only  two-thirds  of  the  thickness 
of  the  cartilage  is  usually  infiltrated,  although, 
exceptionally — as  shown  by  Cornil  and  Ranvier — 
the  whole  cartilage  may  be  infiltrated.  With  regard 
to  the  exact  relation  of  the  uratic  deposit  to  the 
various  elements  of  articular  cartilage,  the  cartilage 
cells  are  held  to  be  the  centres  of  primary  deposit 
by  Cornil  and  Ranvier,  Charcot,  Rindfleisch,  Budd, 
and  Garrod.  Cornil  and  Ranvier  consider  that 
nutritive  disturbances  in  the  cartilage  cells  precede 
the  deposition  of  sodium  urate.  Rindfleisch  and 
Budd,  however,  consider  that  the  cartilage  cells 
do  not  take  any  active  part.  Some  observers,  in- 
cluding Sir  Dyce  Duckworth,  consider  that  the 
deposition  occurs  quite  indiscriminately,  not  select- 
ing for  its  original  site  any  particular  element  of 
the  cartilage.  Others,  as  Bramson,  Rokitansky, 
and  Auguste  Foerster,  think  that  urates  deposit  in 
the  intercellular  cartilaginous  substance. 

*  "Die  Natur  und  Behandluno-  der  Gicht,"  1882. 


92 


CHAPTER  YIT. 

Caufies  affecthig  the  deposition  of  sodium  hivrale — 
Reasons  for  the  special  selection  oj  the  great  toe  and 
ear  as  seats  of  gouty  deposits — Cause  of  the  inflam- 
mation  accoiyipa vying  the  gouty  paroxysm. 

DEPOSITION  OF  SODIUM  BIURATE  ENCOURAGED  BY 
CONCENTRATION   OF   MEDIUM  AND  PROPORTIONS 

OF    SODIUM    SALTS    PRESENT. 

Sir  William  Roberts  found  that  sodium  binrate 
is    very    sparingly    soluble   in    blood    serum ;     at 
blood   heat    the   amount    dissolved   is    about   one 
part   in  10,000  (about   one-tenth  of  its  solubility 
in    Avater).      This    lessened    solubility    is    entirely 
due   to    the   saline   ingredients   of  the   serum,   as 
on  depriving  the  serum  of  its  salts  by  dialysis,  it 
was  then  found  to  exercise  the  same  solvent  action 
on   the    biurate    as    simple   water.       Sir   AVilliam 
Roberts   foimd   that   the    sodium    salts   especially 
diminish  the  solvent  power  of  a  medium  on  sodium 
biurate,  and  that  tliis  diminished  power  is  mainly, 
if  not  entirely,  due  to  the  sodium,  and  is  apparently 
not  much,  if  at  all,  influenced  by  the  acids  com- 
bined with  it,  since  solutions  of  sodium  bicarbonate, 
chloride,  sulphate,  phosphate,  and  salicylate,  pre- 
pared so  that  the  percentage  of  sodium  in  them 
was    the   same,   exhibited   the   same   low   solvent 
action.      His   experiments    also    show   that    if    a 


Deposition  of  Sodium  Bi urate  93 

medium  be  rich  in  urates,  but  poor  in  sodium 
salts,  its  tendency  to  precipitation  is  feeble,  and 
vice  versa.  Since  structures  belonsfino-  to  the  con- 
nective-tissue  class  are  rich  in  sodium  salts  and  are 
also  liable  to  uratic  deposits,  while  muscle,  brain, 
liver,  and  spleen  are  poor  in  sodium  salts  and  not 
liable  to  uratic  deposits,  he  considers  that  the  pro- 
portion of  sodium  salts  in  a  tissue  is  an  important 
factor  in  determining  the  deposition  of  urates  in 
that  tissue. 

PRECIPITATIOX    OF    S0DIU3I    BIURATE    FilOM 
SYNOVIAL    FLUID. 

Another  factor  in  facilitating  the  precipitation 
of  urates  is  to  be  found  in  the  sj-novial  fluid. 
Sir  William  Roberts's  view  is  that  the  uratic  pre- 
cipitation actually  takes  place  from  the  synovial 
fluid,  and  does  not  originate  in  the  cartilaginous 
substance.  This  view  is  based  in  part  on  the 
microscopic  appearance  of  vertical  sections  of  gouty 
cartilage,  in  which  the  deposit  is  seen  to  be  greatest 
on  the  synovial  surface  of  the  cartilage  and  to  be- 
come gradually  sparser  and  sparser  towards  the 
deeper  layers,  and  in  part  on  the  fact  that  synovial 
fluid  has  been  repeatedly  found  heavily  laden  with 
crj'stals  of  sodium  biurate.  He  considers  (as 
opposed  to  Ebstein's  view)  that  the  process  of 
deposition  in  the  cartilage  is  a  purely  passive  and 
physical  one,  and  that  the  synovial  fluid,  charged 
with  its  dissolved  urate,  penetrates  hy  liquid 
diti'usion  into  the  superficial  layers  of  the  car- 
tilage, and  that,  when  the  criticpJ  moment  arrives. 


94  The  Pathology  of  Gout. 

precipitation  takes  place  simultaneously  in  the  s}^- 
novia  and  in  the  cartilage.  According  to  this  view, 
the  after- consequences  are  entirely  secondary,  and 
are  due  to  inflammation  set  up  by  the  presence  of 
the  foreign  body  in  the  tissue. 

As  regards  the  varying  liability  of  diflferent 
joints  to  gouty  attacks,  Sir  William  Roberts  con- 
siders that  it  is,  at  all  events,  in  part,  dependent  on 
a  greater  concentration  of  the  synovia  of  some 
joints,  and  on  a  variable  proportion  of  sodium  salts 
and  possibly  of  sodium  biurate.  The  experiments 
made  by  Frerichs^  on  the  comparative  composition 
of  the  synovia  of  animals  leading  idle  and  active 
existences  somewhat  support  this  view.  Frerichs 
found  that  the  synovia  of  stall-fed  horses  and  oxen, 
leading  an  idle  existence,  was  more  watery  and 
contained  a  larger  proportion  of  sodium  salts  than 
the  synovia  of  similar  animals  doing  work  or  roam- 
ing in  the  meadows.  Moreover,  the  joints  of  the 
idle  animals  contained  twice  as  much  synovia  as 
the  joints  of  similar  animals  taking  active  exercise. 

DEPOSITION   OF   SODIUM   BIURATE    ENCOURAGED   BY 
SLUGGISH   MOVEMENT   OF   MEDIUM. 

It  is  highly  probable  that  the  very  sluggish  move- 
ment of  fluids  in  the  cartilag^inous  and  fibrous  tissues 
favours  the  deposition  of  urates  from  the  medium 
in  which  they  are  dissolved.  As  illustrating  the 
fact  that  whatever  interferes  with  the  movement  of 
the  animal  fluids  favours  the  production  of  gouty 

*  K.  Wagner's  "  ILmdw  orti-ibuch  der  FJiysiologie,"  1884,  Bainl 
iii.,  Part  i.,  pp.  463-466. 


Deposition  of  Sodium  Biurate.         95 

symptoms,  or  of  an  actual  attack  of  gout,  an  in- 
teresting case  has  been  recorded  by  Charcot,^  who 
observed,  in  ahemiplegic  woman  of  forty,  that  most 
of  the  articular  cartihiges  on  the  right,  paralysed, 
side  were  infiltrated  with  urates,  whereas  those  of 
the  non-paralysed  side  showed  no  such  deposits.  Sir 
William  Roberts  considers  that  the  chief  reason 
why,  in  the  post-mortem  room,  the  cartilages  figure 
more  prominently  than  the  fibrous  structures  as 
the  scat  of  deposition  of  sodium  biurate  is  to  be 
found  in  the  fact  that  in  the  fibrous  tissues  there  is 
a  comparatively  free  lymph  How,  which  exercises  a 
more  effective  solvent  action  on  uratic  deposits  than 
can  be  effected  by  the  sluggish  lymph  How  in  the 
cartilao^es.  With  regard  to  the  reason  or  reasons 
that  gouty  precipitation  takes  place  preferentially 
in  synovia  rather  than  in  the  seriun  of"  blood  and 
lymph.  Sir  W.  Roberts  considers  that  the  motion- 
less condition  of  synovia  as  compared  with  the 
state  of  rapid  movement  of  blood  and  lymph  would 
give  to  synovia  a  priority  in  uratic  precipitation. 
In  addition  it  is  possible  that,  as  Sir  Alfred  Garrod 
suggests,  there  is  some  special  attraction  in  the 
joints  for  uric  acid. 

DEPOSITION    OF    SODIUM    BIURATE    ENCOURAGED    BY 
NERVOUS   INFLUENCES. 

It  is  possible,  given  the  condition  in  which 
there  is  a  fair  amount  of  sodium  quadriurate  or 
biurate  circulatino-  in  the  blood,  the  amount  not 


*  "]\raladies    des   Yieillards    et    les    Maladies    chroniques, 


1874 


g6  The  Pathology  of  Gout. 

being  quite  up  to  saturation  point,  that  nervous 
influences  may  accelerate  deposition  of  sodiunl 
biurate.  It  is  well  known  that  whatever  pro- 
duces depression  of  the  nervous  system,  such  as 
excessive  exercise  carried  to  the  point  of  fatigue, 
rage,  fright,  worry,  excitement  or  venereal  excess, 
may  cause  an  attack  of  gout  in  a  gouty  subject.  It 
appears  to  me  that  a  possible  explanation  of  this 
result  is  that  nervous  influence  affects  the  kidneys 
and  depresses  their  excretory  poAver  for  uric  acid, 
which  is  consequently  absorbed  into  the  general 
circulation  and  rapidly  raises  the  quantit}'  of  urate 
in  the  blood  to  the  point  of  over  saturation.  Prob- 
ably the  well-known  effect  of  an  exposure  to  cold 
inducing  a  paroxj'sm  of  acute  gout  is  due  to  a 
similar  cause. 

DEPOSITIOX    OF    SODIUM    BIURATE    ENCOUllAGED    BY 
ABNORMAL   CONSTITUENTS   OF   THE    BLOOD. 

As  previously  stated,  in  cases  of  chronic  lead- 
poisoning  there  is  a  deficient  excretion  of  uric  acid 
in  the  urine  and  an  accuuudation  of  it  in  the  blood. 
As  to  the  natural  way  in  which  the  lead  favours  or 
hastens  tiie  deposition  of  sodium  biurate  and  so 
produces  gout,  there  are  different  opinions.  Sir 
William  Koberts  ^  considers  that  it  is  difficult  to 
believe  that  lead-poisoning  produces  the  same  con- 
stitutional diathesis  as  that  which  exists  in  true 
gout,  and  prefers  to  think  that,  while  gout  and 
plumbism  differ  in  all  other  respects,  they  have  one 

*  "Transactions  of  the  Medical  Society,"  vol.  xiv.,  d.  88. 


Gout  and  Plumb  ism.  97 

tx3nd€ncy  or  vice  in  common,  namely,  the  tendency 
to  uratosis — that  is,  to  the  deposition  of  sodium 
biurate.  He  considers  it  is  more  accurate,  instead 
of  speaking  of  ordinary  gout  and  satiiniine  gout, 
to  speak  of  gouty  uratosis  and  saturnine  uratosis. 
It  appears  to  me  that  gout  and  plumbism  have 
more  in  common  than  this  tendency  to  uratosis 
— that  is,  to  the  deposition  of  sodium  biurate — in 
that  they  both  have  the  same  tendency  to  cause 
the  presence  of  an  excess  of  urates  in  the  blood. 
The  association  of  lead-poisoning  with  gout  has 
been  repeatedly  observed,  but  Oliver  *  states  that 
in  the  north  of  England  this  intimate  relationship 
between  gout  and  lead-poisoning  is  not  seen.  He 
is  not  satisfied  that  the  reason  why  gout  is  so  little 
kno^vn  in  the  north  as  a  symptom  of  lead -poisoning, 
while  it  is  so  common  in  the  south,  is  entirely  due 
to  the  difference  in  the  drinking  habits  of  the 
people — whisky  being  the  general  alcoholic  drink 
in  the  north  and  malt  liquor  in  the  south.  At 
the  same  time  he  confesses  his  inability  to  ofier  any 
further  explanation. 

I  am  of  opinion  that  the  influence  of  lead 
in  producing  gout  depends  solely  on  the  extent  to 
which  the  kidney  parenchyma  is  damaged.  With 
much  damage  done  to  the  kidney  cells,  w^hose 
function  it  is  to  excrete  uric  acid,  absorption  of 
quadriurate  into  the  blood  occurs ;  the  subsequent 
development  of  an  attack  of  gout  entirely  depends 
on  the  amount  of  absorbed  quadriurate,  which  in  its 
turn  depends  on  the  amount  of  kidney  mischief 

*  Goulstonian  Lectures  on  "Lead  Poisoning,"  189L 
H 


98  The  Pathology  of  Gout. 

deposition  of  sodium  biurate  encouraged  by 
injury  to  joints  or  by  interference  with 
their  nutrition. 

A  slight  injury  to  a  joint,  which  in  a 
healthy  person  would  speedil}^  pass  off,  in  a  gouty 
person  renders  the  part  susceptible  to  the  deposition 
of  sodium  biurate  if  sodium  qnadrinrate  be  cir- 
culating in  the  blood.  This  susceptibility  is  prob- 
ably in  some  way  connected  with  an  impairment  of 
the  nutrition  of  the  affected  tissues.  Fagge,  indeed, 
regarded  a  paroxysmal  attack  of  gout  in  the  light 
of  an  accident  occurring  in  the  course  of  an  essen- 
tially chronic  change  in  the  joint  affected. 

As  regards  the  relation  between  gout  and 
rheumatism.  Sir  Alfred  Garrod  has  remarked  that 
if  gout  supervene  in  individuals  who  have  suffered 
from  rheumatism,  it  is  generally  the  articulations 
which  were  the  seat  of  rheumatism  that  are 
Urst  attacked  by  gout.  So  that  joints  Avhich 
have  been  the  seat  of  acute  rheumatism  are 
especially  predisposed,  in  gouty  subjects,  to  be- 
come the  seat  of  uratic  deposits.  Dr.  Latham  "^ 
thinks  it  is  probable  that  the  uric  acid  cir- 
culating in  the  blood  might  exert  a  toxic  effect 
on  certain  portions  of  the  spinal  cord  which 
control  the  nutrition  of  the  joints,  and  so  cause 
nutritive  changes  or  inflammation  in  the  joints 
connected  with  that  portion  of  the  cord.  As  a 
result  of  the  inflammation  or  nutritive  changes  in 
the  joints,  sodium  biurate  deposits  in  them  or  in  the 
tissues  around  the  affected  joints. 

*  "  Croonian  Lectures,"  1886. 


Views  of  U ratio  Deposition,  99 

Ebstein^  considers  that  deposition  of  sodium 
biurate  is  dependent  on  and  is  produced  by  previous 
necrosis  of  the  affected  tissues,  and  that  the  uratic 
deposit  never  occurs  in  a  normal  tissue.  His  view  is 
that  the  neutral  sodium  urate  circulating  in  the  blood 
acts  as  an  irritant  and  produces  necrosis  of  the  car- 
tilages or  other  tissues,  in  which  the  sodium  biurate 
is  subsequently  deposited ;  as  a  result  of  this  necrosis 
he  considers  that  an  acid  is  developed  which  converts 
the  neutral  urate  into  acid  urate,  which  compound  is 
then  deposited  in  the  necrosed  areas.  This  theory 
is  obviously  an  erroneous  one,  since  the  neutral 
sodium  urate  cannot  exist  in  the  circulation  {see 
p.  17).  Klempererf  does  not  consider  that  uric  acid 
is  responsible  for  the  necrotic  changes  in  tissues, 
nor  that  the  phenomena  of  gout  can  be  due  to 
mere  crystallisation  of  sodium  biurate  from  the 
blood,  because  in  leucocythsemia,  where  an  excess 
of  urate  is  present  in  the  blood,  neither  local 
necrosis  nor  uratic  deposits  occur.  He  believes 
that  some  unknown  substances,  in  gout,  lead  to 
inflammatory  and  necrotic  processes  in  various 
tissues ;  these  necrotic  areas  then  attract  the  uric 
acid  from  the  blood,  the  chemical  affinity  of  the 
necrotic  parts  for  uric  acid  being  so  great  that  the 
blood  cannot  re-dissolve  it.  Yon  Noorden  thinks 
the  unknown  substance,  which  starts  the  inflam- 
matory and  necrotic  processes  is  a  ferment,  and 
that  the  uric  acid  crystallises  out  in  the  necrotic 
tissues. 

*  *'  Die  Natur  und  Behandlung  der  Gicht,"  1882. 

f  Deutsche  medici/nisehe  W&chenschrift,  1895,  vol.  xxi.,  p.  ^bb>^ 


ioo  The  Pathology  of  Gout, 

DEPOSITION   OF   SODIUM  BIURATE  NOT  AFFECTED   BY 
DIMINISHED   ALKALINITY   OF   THE   BLOOD. 

A^arious  writers  have  put  forward  the  opinion  that 
uratic  deposition  is  dependent  upon  a  diminution 
of  the  alkaUnity  of  the  blood.    Mordhorst"^  considers 
that  the  tissues  affected  by  gout  are  less  alkaline 
than  the  blood,  and  that,  if  the  alkalinity  of  the 
latter  becomes  lowered,  then  deposition  may  take 
place.     Dr.  Haig  considers  that  diminished  alka- 
linity of  blood   causes   deposition  of  uric  acid   in 
the   liver,  spleen,   fibrous  tissue,   and  joints,   and 
that  increased   alkalinity  of  the  blood  causes  its 
re-solution.     The  view  that  diminished  alkalinity 
of  the   blood   causes   uratic   deposition,   and   that 
increased  alkalinity  of  the  blood  causes  re-solution 
of  the  uratic  deposits,  is  in  my  opinion  erroneous 
and  untenable  for  the  following  reasons  : — (1)  The 
Adew   is   apparently   based   on    the   deposit   being 
uric  acid,  whereas  it  is  sodium  biurate,  the  solution 
of  which,  as  Sir  William  Roberts  has  shown,  is  not 
increased   by    increased   alkalinity   of  the   blood ; 
(2)  the  occurrence  of  a  gouty  attack  is  not  neces- 
sarily   accompanied    by    any   diminution   in    the 
alkahnity  of  the  blood  {see  pp.  129, 130) :  and  (3)from 
a  series  of  experiments  that  I  have  conducted,  and 
which  will  be  subsequently  described,  it  appears 
that  a  diminution  of  the  alkalinity  of  a  medium 
does   not  affect  the  deposition  of  sodium  biurate 
from  that  medium. 

*  "  Vorhandlungen  des   Congress  fur  Innere  Medicin/'  1896, 
1).  405. 


Gouty  Deposits  in  Great  Toe.        ioi 

reasons  for  the  special  selection  of  the 
great  toe  and  ear  as  seats  of  gouty 
deposits. 

There  are  several  reasons  to  account  for  the 
special  causation  of  uratic  deposits  in  the  great  toe. 
(1)  There  is  the  liability  of  the  metatarso-phalangeal 
joint  to  injury  from  having  to  support  the  weight 
of  the  body,  and  from  being  subjected  to  sudden 
shocks.  (2)  The  remoteness  of  the  joint  from 
the  heart,  and  the  force  of  the  circulation  being 
consequently  at  its  minimum  at  that  part.  (3)  The 
poor  vascularity  of  the  tissues  of  the  joint.  The 
liability  of  the  joint  to  injury  is  shown  by  Garrod's 
examinations  of  the  great-toe  joints  of  twenty 
subjects  known  not  to  have  had  gout.  In  fourteen 
he  found  ulceration  of  the  cartilages  of  one  or 
both  joints.  Of  these  twenty  subjects  three  were 
under  thirty  years  of  age  and  showed  no  ulceration 
of  the  cartilages ;  the  remaining  seventeen  were 
over  thirty  years  of  age,  and  of  these  fourteen, 
or  82  per  cent.,  showed  ulceration  of  the  cartilages. 
All  the  subjects  over  fifty  years  of  age  showed 
ulceration. 

In  the  helix  of  the  ear  the  slusfS'ish  circulation 
and  the  coldness  of  the  organ  are  quite  sufficient 
to  account  for  the  frequency  with  which  uratic 
deposits  are  found  in  that  part. 

CAUSE   OF   THE   INFLAMMATION  WHICH  ACCOMPANIES 
THE   GOUTY   PAROXYSM. 

The  gouty  paroxysm  is  due  to  precipitation  of 
sodium  biurate,  which  always  takes  place  in    the 


102  The  Pathology  of  Gout. 

crj'stalline  form,  the  crystals  being  distributed 
through  the  impHcated  tissue  in  the  form  of 
delicate  needles,  aggregated  into  tufts,  bundles, 
and  stars.  When  deposition  occurs  in  cartilage 
the  crystalline  deposit  acts  as  an  irritant  and 
causes  inflammation  leading  to  proliferation  and 
necrosis  of  cartilage  cells,  which  may  be  followed 
by  erosion  of  cartilage  and  of  uratic  deposits, 
and  consequent  displacement  of  the  latter  into 
the  cavity  of  the  joint.  Along  the  borders 
of  the  cartilage,  where  the  deposits  are  com- 
paratively small  and  the  tissues  are  relatively 
rich  in  capillary  vessels,  the  inflammatory  processes 
may  produce  a  more  luxuriant  growth  of  the 
cartilage  cells,  resulting  in  the  formation  of 
occhondroses  at  the  margins  of  the  articulation. 
Although  I  consider  that  the  inflammatory  part  of 
the  gouty  attack  is  secondary  to  the  deposition 
of  sodium  biurate  crystals,  yet  it  must  be  granted 
that  such  deposition  should  occur  fairly  copiously 
and  suddenly  in  order  to  start  the  inflammatory 
process.  Undoubtedly  the  biurate  may  deposit 
slowly  and  quietly  in  joints  without  the  develop- 
ment of  any  acute  attack,  or  for  some  time 
antecedent  to  the  development  of  an  acute  attack. 
The  observations  of  IMoxon  and  Fagge  support 
the  conclusion  that  the  discovery  after  death  of 
uratic  deposits  in  a  joint  is  not  always  to  be 
regarded  as  a  certain  proof  that  the  joint  has 
passed  through  an  inflammatory  gouty  attack. 
Sir  Alfred  Garrod's  views,  which  are  shared  bj^ 
Sir  William  Roberts  and  supported  by  abundant 


General  Coxclusions.  103 

evidence,  are  in  favour  of  the  deduction  that  the 
deposition  of  the  crystalline  biurate  is  not  merely 
an  accompaniment,  but  is  the  direct  cause  of  the 
joint  troubles  of  gout.  It  is  therefore  of  practical 
importance  to  know  what  are  the  various  factors 
or  conditions  which  may  influence  the  conversion 
of  sodium  quadriurate  into  biurate,  which  ma}' 
alter  the  solubility  of  sodium  biurate  in  the  blood, 
lymph,  and  synovia,  and  which  may  affect  the 
precipitation  of  the  sodium  biurate.  These  points 
will  be  dealt  with  in  Part  III. 

GENERAL  COXCLUSIONS  AS  TO  THE  PATHOLOGY  OF 

GOUT. 

The  main  points  and  conclusions  arrived  at 
in  the  preceding  account  of  the  pathology  of 
gout  are  as  follows  : — 

1.  Uric  acid  is  not  normally  present  in  the 
blood  of  man  and  other  mammals,  nor  in  the 
blood  of  birds. 

2.  Uric  acid  is  normally  produced  only  in  the 
kidneys. 

3.  Uric  acid  is  normally  foraied  from  urea, 
probably  by  conjugation  of  that  substance  with 
glycocine  in  the  kidneys. 

4.  Uric  acid  is  present  in  the  blood  in  gout 
as  the  soluble  sodium  quadriurate.  In  its  soluble 
form  it  is  not  a  toxic  agent.  It  deposits  from 
the  blood  as  sodium  biurate,  which  acts  passively 
and  physically  as  a  foreign  body  ia  the  tissues 
or  organs  in  which  it  is  deposited. 

5.  The  presence   of  uric  acid  in  the  blood  in 


I04  The  Pathology  of  Gout. 

gout  is  dae  to  its  deticient  excretion  by  the  kidnej^s, 
and  to  the  subsequent  absorption  of  the  non- 
excreted  portion  into  the  blood  from  those 
organs. 

6.  Gout  is  probably  always  preceded  by  some 
affection  of  the  kidneys,  functional  or  organic, 
which  interferes  ^vith  the  pro2>er  excretion  of  uric 
acid.  The  probable  seat  of  the  kidney  aft'ection 
giving  rise  to  gout  is  in  the  epithelium  of  the 
convoluted  tubes. 

7.  In  certain  blood  diseases  and  disorders 
accompanied  by  leucocytosis  uric  acid  is  formed 
within  the  system  from  nuclein.  In  such  circum- 
stances it  passes  at  once  into  the  blood  and  is 
rapidly  eliminated  by  the  kidneys. 


105 


lart  II. 


iETIOLOGY  OF  GOUT  —  THE  VARIOUS 
FORMS  OF  GOUT  AND  THEIR  CLIN- 
ICAL FEATURES  —  DIAGNOSIS  AND 
PROGNOSIS. 

CHAPTER    VIIL 

jEtiology  of  gout — Predisposing  causes  of  gout — Exciting 
causes  of  gmit — Acute  gout — Chronic  gout — Satur- 
nine or  lead  gout — Irregular  or  aharticular  gout. 

MUlOUyOY   OF   GOUT. 

Ag"e. — Gout  is  mainly  a  disease  of  middle  and 
late  life,  but  it  may  occur  earlier  if  there  is  a 
marked  hereditary  tendency. 

Sex. — Gout  is  much  more  common  among 
males.  This  tendency  is  no  doubt  mainly  due  to 
the  fact  that  the  habits  of  men,  with  regard  to  diet 
and  alcoholic  drinks,  are  more  conducive  to  the 
development  of  the  disease  than  the  more  tem- 
perate habits  of  life  of  the  majority  of  women. 

Hereditary  predisposition. — This  is  the  most 
important  factor  in  the  development  of  gout.  The 
females  of  gouty  families  frequently  escape  the 
apparent  development  of  gout  in  themselves,  but 
transmit  the  disease,  or  the  liability  to  it,  to  their 
children.  It  is  doubtful,  however,  whether  true 
atavism   occurs  in  connection  with  gout ;  that  is. 


io6  The  Etiology  of  Gout. 

whether  gout  entirely  misses  a  generation.  It  is 
more  probable  that  it  appears  in  some  form, 
irregular  or  otherwise,  in  the  generation  that  it 
is  supposed  to  have  passed  over. 

Habits  of  life.^The  abuse  of  alcohohc  drinks, 
especially  those  of  the  fermented  class,  such  as 
wines  and  beers,  and  the  excessive  consumption 
of  nitrogenous,  rich,  and  indigestible  food,  are 
powerful  factors  in  the  development  of  gout. 
Indolent  habits  and  inadequate  physical  exercise 
also  strongly  predispose  to  gout. 

Lead-poisoning. — Chronic  lead-poisoning  pre- 
disposes to  gout,  most  probably  by  causing  a 
chronic  affection  of  the  kidneys,  which  interferes 
with  the  proper  elimination  of  uric  acid  by  those 
organs. 

Uric-acid  gravel  in  the  kidneys. — Those  who 
suffer  much  in  early  life  from  uric-acid  gravel  are 
also  prone  in  later  life  to  develop  gout.  The 
reason  for  this  liability  probably  is  that  the 
deposits  of  uric  acid,  which  no  doubt  in  such 
circumstances  occur  in  the  kidneys,  produce  that 
pathological  condition  of  those  organs  which,  by 
interfering  with  the  proper  elimination  of  uric  acid 
by  the  kidneys,  constitutes  the  starting-point  of 
gout. 

Immediate  exciting  cause. — An  attack  of  acute 
gout  is  frequently  induced  by  unusual  indulgence 
in  food  or  drink,  or  by  some  powerful  emotion — 
such  as  a  fit  of  anger,  worry,  or  anxiety,  or  by 
exposure  to  cold,  or  by  the  receipt  of  some  injury. 
For  the  production  of  gout,  whether  of  the  regular 


Acute  Gout.  icy 

(articular)  or  irregular  (abarticular)  type,  the 
deposition  of  sodium  biurate  in  the  organ  or  tissue 
affected  is,  in  my  opinion,  essential.  The  mere 
presence  of  uric  acid  in  the  blood  in  the  lorm  of  the 
sodium  quadriurate  is  insufficient  for  the  produc- 
tion of  any  form  of  gout,  in  the  absence  of  deposi- 
tion of  the  biurate  from  the  fluids  of  the  bod3\ 
That  such  is  the  case  is  illustrated  by  those  blood 
disorders,  such  as  leucocyth^emia  and  severe 
amiemia,  in  Avhich  the  blood  is  laden  with  uric 
acid,  and  yet  no  symptoms  of  cither  regular  or 
irregular  gout  arise.  The  absence  ot  such  symptoms 
is  due  to  the  fact  that  the  uric  acid,  which  is 
present  in  the  blood  as  sodium  quadriurate,  is 
completely  and  lapidly  eliminated  by  the  kidneys 
before  there  is  time  for  the  formation  and  deposi- 
tion of  the  biurate. 

THE  VARIOUS  FORMS  OF  GOUT  AND   THEIR   CLINICAL 

FEATURES. 

ACUTE     GOUT. 

A  slow  deposition  of  sodium  biurate  within  the 
joints,  accompanied  by  twinges  of  pain,  may  oc- 
casionally precede  the  acute  attack,  but,  as  a  rule, 
no  warning  ushers  in  the  first  attack  of  gout,  and 
the  individual  usually  feels  in  good  health  just 
prior  to  the  attack.  Subsequent  attacks,  however, 
may  be  preceded  by  symptoms  of  dyspepsia, 
constipation,  mental  depression,  or  loss  of  appetite. 

The  seizure  of  acute  gout  most  frequently 
occurs  in  the  early  hours  of  the  morning,  but  may 


io8         The   Various  Forms  of  Gout. 

come  on  at  any  hour  of  the  day  or  night.  Usually 
between  the  hours  of  one  and  four  in  the  mornincr 
the  patient  is  awakened  by  severe  pain,  generally 
in  the  great  toe,  sometimes  in  the  ankle,  instep, 
heel,  or  knee.  Slight  shivering  attacks  and  a 
little  elevation  of  temperature  may  follow.  The 
pain  increases  in  intensity,  so  that  the  slightest 
jarr'ng  of  the  affected  part  may  cause  extreme 
torture.  After  some  hours  partial  abatement  of 
the  pain  occurs,  and  is  accompanied  by  gentle 
perspiration.  In  the  morning  the  toe  is  swollen, 
the  skin  is  tense,  shiny,  and  extremely  tender,  and 
the  veins  are  distended.  On  the  second  night 
the  severity  of  the  pain  may  recur,  and  such 
recurrences  may,  in  the  absence  of  suitable  treat- 
ment, occur  for  many  days.  The  pain  in  the 
joint  is  excruciating,  and  is  quite  out  of  proportion 
to  the  external  signs  of  inflammation.  When  the 
attack  is  subsiding  the  swelling  and  redness  of 
the  affected  part  lessen,  the  skin  itches  and  pits  on 
jDressure,  and  desquamation  follows.  Sir  Willoughby 
Wade  ^  has  pointed  out  that  in  an  acute  attack 
of  gout  in  the  great  toe  a  line  of  tenderness 
extends  from  the  base  of  the  great  toe  across 
the  foot  to  the  outer  side.  This  line  is  the 
site  of  a  nerve-trunk,  Avhich  is  distributed  to  the 
periphery  of  the  gi-eat  toe.  The  cause  of  the 
tenderness  is  probably  due  to  a  deposition  of 
sodium  biurate  in  the  nerve  sheath,  or  in  the 
nerve  itself  The  oedema  around  the  joint  is 
characteristic,  and   is  of  great   assistance   in   dio- 

*  lii-it.  Mad.  Joiirn.,  1897,  i.,  p.  509. 


Acute  Gour.  109 

tinf^uishing  the  affection  from  rheumatism.  Gouty 
inflammation  of  a  joint  is  not  followed  by  supjjura- 
tion.  The  temperature  most  commonly  ranges 
from  99°  to  102°  F.,  and  the  attack  is  generally 
accompanied  by  thirst,  anorexia,  and  constipation, 
whilst  the  urine  is  scanty,  high-coloured,  and 
usually  deposits  amorphous  urates  on  cooling. 
Temporary  albuminuria  has  been  frequently 
observed  during  the  early  stages  of  an  attack  of 
acute  gout,  and  occasionally,  slight  albuminuria 
lasts  throughout  the  attack,  owing  to  the  affection 
of  the  kidneys  which  constitutes  the  primary  cause 
of  the  gout. 

An  attack  of  acute  gout  lasts  on  an  average 
from  eight  to  fourteen  da3^s  in  persons  of  strong 
constitution,  but  with  advancinof  ao-e  the  duration 
of  the  attack  becomes  prolonged.  A  first  attack 
of  gout  may  not  be  followed  by  another,  provided 
attention  be  paid  to  diet  and  to  the  general  mode 
of  life.  On  the  other  hand,  frequent  recurrences 
may  occur.  At  first  the  attack  of  gout  is  most 
liable  to  occur  towards  the  end  of  winter  or  begin- 
ning of  spring,  but  after  repeated  annual  attacks 
at  the  period  mentioned,  autumnal  attacks  may 
be  added,  or  even,  in  exceptional  cases,  summer 
attacks.  Although  the  majority  of  first  attacks 
of  gout  occur  in  the  great- toe  joint,  yet  the  disease 
may  start  in  other  joints,  of  which  those  most 
commonly  so  affected,  placing  them  in  their  order 
of  liability  to  such  attacks,  are  the  ankles,  the 
knees,  the  small  hand-joints,  the  elbows,  and, 
rarely,  the  shoulders  and  hips.     The  selection  of 


1 10         The   Various  Forms  of  Gout. 

any  particular  joint  for  a  primary  attack  is  no 
doubt  dependent  on  slight  inflammatory  or  trophic 
changes  in  the  particular  joint  from  some  recent 
injury  or  strain. 

Cases  of  typical  acute  gout  are  now  much  less 
frequent  than  they  were  in  the  days  when  the 
disease  was  so  graphically  described  by  Sydenham. 
This  is  mainly  due  to  the  greater  temperance  in 
eating  and  drinking  which  prevails  in  the  present 
age,  and  in  part,  no  doubt,  to  the  spread  of 
athleticism,  and  to  the  development  of  healthy 
outdoor  exercises.  Still  in  many  cases  the  faults 
of  the  ancestors  have  transmitted  to  their  descend- 
ants a  tendency  to  the  minor  forms  of  gout,  which 
frequently  require  treatment  at  the  hands  of  the 
physician. 

CHRONIC   GOUT. 

"With  the  earlier  attacks  of  gout  it  is  not 
usual  ior  more  than  one  or  two  joints  to  be 
affected,  but  after  repeated  seizures  a  number 
of  joints  may  become  involved.  As  the  recur- 
rence of  gout  becomes  more  frequent  the  attacks 
also  become  more  prolonged,  and  last  for  weeks 
or  even  months  unless  efficacious  treatment  is  re- 
sorted to.  In  chronic  gout  the  deposits  of  sodium 
biurate  linger  in  the  joints,  leading  to  deformities 
and  crippling  of  the  parts.  Slight  recurrences 
readily  occur,  and  various  forms  of  irregular  gout 
may  then  become  added  to  the  gouty  condition. 

In  the  subjects  of  chronic  gout  tophi  are  apt 
to  form  in  various  localities ;  these  deposits  are 
most  frequently  seen  in  the   male  sex,  and  con- 


Chronic  Gout.  i  i  i 

stitute  the  so-called  tophaceous  gout.  These  tophi 
consist  mainly  of  deposits  of  sodium  biurate  under 
the  skin,  and  are  principally  found  in  the  auricles 
of  the  ears,  in  the  vicinity  of  joints,  and  in  bursne 
over  joints.  If  excessive  accumulation  of  the 
biurate  occurs,  these  tophi  assume  a  great  size, 
and  may  then  cause  the  integument  to  give  way, 
when  a  discharge  of  a  thick  creamy  fluid  containing 
an  abundance  of  crystals  of  sodium  biurate  takes 
place.  The  swelling  in  the  vicinity  of  a  joint  may 
give  rise  to  fluctuation,  but  such  swelling  should 
never  be  opened.  Tophi  may  communicate  with 
a  joint,  or  may  be  situated  beneath  the  skin  and 
remote  from  a  joint. 

Considerable  enlargement  and  deformity  of 
jomts  may  occur  in  connection  with  chronic  gout 
to  which  the  deposits  of  sodium  biurate  only  con- 
tribute in  small  part.  In  such  cases  the  enlarge- 
ment is  due  to  thickening  of  the  synovial  membrane, 
and  to  overgi'owth  of  the  cartilages  and  of  the  ends 
of  the  bones.  This  form  constitutes  the  so-called 
cl ironic  deforming  gout.  Permanent  deformity 
of  the  affected  joints  may  result,  and  partial  dis- 
locations and  ankyloses  may  also  occur.  On  the 
other  hand,  the  uratic  deposits  may  undergo 
complete  solution,  and  the  joint  be  left  in  an 
apparently  normal  condition. 

THE   KIDNEYS   IN    CHRONIC   GOUT. 

When  chronic  gout  is  accompanied  by  much 
deposition  of  biurate  it  is  a  sure  indication  that  the 
kidneys  are  incapable  of  excreting  the  whole  of  the 


112  The   Various  Forms  of  Gout, 

uric  acid  formed  in  them,  and  that  consequently 
daily  absorption  of  the  non-excreted  portion  is  oc- 
curring into  the  general  circulation.  In  such  cases 
a  most  careful  and  systematic  examination  of  the 
urine  should  be  made.  The  urine  of  chronic  gout 
is  somewhat  increased  in  quantity,  and  is  of  lower 
specific  gravity  and  somewhat  paler  than  normal. 
The  amount  of  uric  acid  eliminated  is  diminished. 
A  trace  of  albumen  is  frequently  present,  and 
permanent  albuminuria  is  a  fairly  common  occur- 
rence in  confirmed  gout.  If  the  renal  condition  is 
allowed  to  become  very  aggravated,  then  cardiac 
failure  follows,  with  pulmonary  congestion,  oedema 
of  the  lungs,  bronchitis,  congestive  enlargement  of 
the  liver,  gastric  catarrh,  dropsy,  and  symptoms  of 
urtemia.  In  such  cases  pneumonia  is  apt  to 
supervene  and  to  be  attended  by  a  fatal  issue. 

THE   HEART    AND  GOUTY   KIDNEY. 

Changes  in  the  heart  and  circulation,  conse- 
quent on  gouty  affections  of  the  kidneys,  are 
indicated  by  hypertrophy  of  the  left  ventricle,  a 
strong  cardiac  impulse,  displacement  of  the  apex 
beat  to  the  left,  loudness  and  occasional  redupli- 
cation of  the  first  sound,  and  accentuation  of 
the  aortic  second  sound.  The  pulse  is  of  high 
tension,  and  the  arteries  are  hard,  tortuous,  and 
sometimes  atheromatous.  Under  such  conditions 
a  cerebral  haemorrhage  may  occur.  If  compensa- 
tion fails  then  dilatation  of  the  heart  occurs,  the 
area  of  dulness  is  greatly  increased,  the  action  of 
the  heart  becomes  rapid,  and  the   usual  signs  of 


Saturxixe  or  Lead  Gout.  113 

backworking   of  the  blood  from  the  left   side   of 
the  heart  follow. 

True  angina  pectoris,  associated  with  widespread 
arterial  degeneration  and  softening  of  the  walls  of 
the  heart,  occasionally  occurs  in  gouty  subjects,  the 
gouty  condition  no  doubt  being  a  powerful  factor 
in  the  production  of  the  degenerative  changes 
leading  up  to  the  anginal  attacks.  Pseudo-angina 
pectoris  unassociated  with  any  general  arterial 
degeneration  also  may  occur  in  the  gouty,  and 
is  accompanied  by  severe  pam  in  the  region  of 
the  heart,  passing  down  the  left  arm,  a  feeling  of 
suffocation,  flatulency,  and  gastric  disturbance. 

SATURNINE    OR   LEAD   GOUT. 

As  previously  described  (see  p.  59),  chronic 
lead-poisoning  gives  rise  to  both  chronic  kidney 
disease  and  gout.  The  cause  of  the  liability  of 
those  suffering  from  chronic  plumbism  to  be 
attacked  by  gout  has  already  been  considered 
{see  pp.  60, 96,  97).  Briefly  stated,  it  most  probably  is 
due  to  the  action  of  lead  salts  on  the  kidney 
epithelium  causing  a  diminution  in  the  excretion 
of  uric  acid,  so  that  consequently  an  absorption 
^f  the  non-excreted  portion  takes  place  from  the 
kidneys  into  the  general  circulation.  This  view 
is  supported  by  the  well-known  fact  that  the 
medicinal  administration  of  lead  salts  notably 
diminishes  the  excretion  of  uric  acid  by  the 
kidneys.  A  prolonged  period  of  lead  intoxication 
— on  the  average  about  twenty-one  years — is 
required  to  produce  true  saturnine  gout. 
I 


114  1^^^   Various  Forms  of  Gout. 

The  patient  suffering  from  saturnine  gout, 
unlike  the  majority  of  sufferers  from  inherited 
gout,  is  pale,  thin,  and  auiemic.  The  gouty  attacks 
are  frequently  repeated  and  affect  many  joints, 
whilst  signs  of  interstitial  nephritis  make  their 
appearance.  If  the  lead-poisoning  has  been  of 
short  duration  the  lesions  may  yield  to  treatment, 
but  after  a  prolonged  absorption  of  lead  into  the 
system  the  kidney  condition  is  generally  incurable. 

IRREGULAR   OR   ABARTICULAR   GOUT. 

Gout  appearing  in  any  situation  other  than  a 
joint  is  regarded  as  irregular  or  abarticular.  Differ- 
ent forms  of  irregular  gout  may  accompany  arthritic 
gout,  or  may  take  its  place,  or  may  alternate  with 
it.  Although  attacks  of  irregular  gout  may  occur 
in  persons  subject  to  articular  gout,  yet  they  more 
frequently  occur  in  those  who  have  never  suffered 
from  gout  in  the  joints,  but  who  are  predisposed  to 
gout  either  by  inheritance  or  by  their  mode  of 
life.  Undoubtedly  the  terms  "irregular  gout" 
and  "  suppressed  gout "  have  frequently  been 
applied  to  pathological  conditions  in  no  Avay  con- 
nected with  gout,  and  it  is  therefore  important 
that  a  diagnosis  of  irregular  gout  should  be  based 
on  good  and  sufficient  grounds. 

The  most  important  points  to  pay  attention 
to  in  the  diagnosis  of  irregular  gout  are  the  question 
of  heredity,  the  habits  of  the  patient,  the  nature  of 
the  attack,  a  careful  examination  of  the  urine  and, 
if  possible,  of  the  blood  or  blood  serum,  and,  lastly, 
the   successful  reaction   to   therapeutic    remedies. 


Irregular  Gout.  i  i  5 

Cramps  and  aching  pains  in  various  muscles  and 
tingling  sensations  in  the  hands  and  feet  are 
frequently  associated  with  irregular  gout.  I  believe 
that  all  forms  of  irregular  gout  are  due  to  the 
precipitation  in  the  crystalline  form  of  sodium 
biurate  in  the  organ  or  tissue  aiYected.  Sir  William 
Roberts  also  considers  it  quite  possible  that  attacks 
of  irregular  gout  are  due  to  the  irritation  produced 
by  deposits  of  sodium  biurate  in  the  affected 
viscera.  Deposits  of  sodium  biurate  have  been 
found  after  death  in  the  valves  of  the  heart,  in  the 
walls  of  arteries  and  veins,  in  the  vocal  cords,  in 
the  mucous  follicles  of  the  pharynx,  in  the  walls  of 
the  bronchial  tubes,  in  the  meninges  of  the  brain 
and  spinal  cord,  and  in  several  other  localities. 
Although  deposits  of  sodium  biurate  have  not  been 
found  in  the  walls  of  the  alimentary  tract,  yet 
it  is  quite  possible  that  such  deposits  might  occur, 
and  either  have  been  overlooked  at  a  post-mortem 
examination,  since  they  would  be  most  difficult  to 
detect,  or  have  undergone  solution  before  death. 


ii6 


CHAPTER    IX. 

Irregular  gout  affecting  the  alimentary  tract — Irregular 
gout  affecting  the  air-2?assages  and  lungs — Irregular 
gout  affecting  the  heart  and  vessels — Irregular  gout 
affecting  the  neroous  system — Irregular  gout  affecting 
the  genito-urinary  system — Irregular  gout  affecting 
tlie  skin — Gouty  glycosuria  and  diabetes — Gouty 
hepatic  congestion — Gouty  affections  of  the  eye  and 
ear — Retrocedent  or  metastatic  gout — Diagnosis  and 
prognosis  of  gout. 

The  various  forms  of  irregular  gout  may  be  con- 
veniently classified   into   the   following  groups: — 

(1)  Irregular  gout  affecting  the  alimentary  tract; 

(2)  irregular  gout  affecting  the  air-passages  and 
lungs;  (3)  irregular  gout  affecting  the  heart  and 
vessels;  (4)  irregular  gout  affecting  the  nervous 
system;  (5)  irregular  gout  affecting  the  genito- 
urinary system;  (6)  irregular  gout  affecting  the 
skin  ;  (7)  complications  and  sequelae  of  gout. 

IRREGULAR  GOUT  AFFECTING  THE  ALIMENTARY 

TRACT 

Gouty  pharyngitis  is  by  no  means  an  uncommon 
condition.  The  mucous  membrane  of  the  pharynx 
is  congested  and  swollen.  The  uvula  assumes 
a  dusky-red  colour  and  is  cedematous.  Gouty 
tonsillitis  may  also  occur. 

Gouty  oesophagismus  occasionally  occurs,  and 
may  be  severe. 


Irregular  Gout,  iij 

Goufy  dyspepsia  is  a  very  common  form 
of  irregular  gout.  It  is  usually  accompanied  by 
excessive  gastric  acidity,  flatulence,  and  heartburn. 
Gastric  pain,  dilatation  of  the  stomach,  and  pyrosis 
are  occasionally  associated  with  this  form  of 
d^^spepsia,  which  is  frequently  of  a  prolonged  and 
obstinate  nature. 

Chronic  gastro-intesfinal  catarrh  is  an  occa- 
sional form  of  irregular  gout.  It  is  generally 
accompanied  by  vomiting,  colic,  and  constipation  ; 
occasionall}'-  diarrhoea  occurs. 

IRREGULAR   GOUT   AFFECTING   THE   AIR-PASSAGES 
AXD    LUXGS. 

Gouty  laryngitis. — Deposits  of  sodium  biurate 
have  been  found  in  the  vocal  cords,  the  ar3^tenoids, 
and  the  crico-ar3'tenoid  ligaments  and  joints. 
Congestion  and  swelling  of  the  mucous  membrane 
occur,  and  the  congestion  may  extend  to  the  vocal 
cords.  The  principal  symptoms  are  hoarseness, 
irritable  cough,  and  scanty  expectoration,  which 
is  occasionally  streaked  with  blood. 

Gouty  tracheitis. — This  affection  is  accompanied 
by  ver}^  irritable  cough  and  scanty  expectoration. 

Acvie  gouty  bronchitis  frequently  precedes  an 
arthritic  attack,  and  often  subsides  when  the 
joints  become  affected.  The  symptoms  of  acute 
gouty  bronchitis  may  be  very  severe,  and  the 
heart's  action  often  becomes  irregular  and  feeble. 
The  expectoration  may  be  blood-stained,  and  the 
dyspnoea  is  frequently  severe. 

Chronic  gouty   bronchitis. — This    affection    is 


ii8         The   Various  Forms  of  Gout. 

accompanied  by  an  irritable  cough  and  scanty 
expectoration.  It  is  especially  liable  to  alternate 
with  arthritic  attacks. 

Goiiiy  asthma. — Attacks  may  alternate  with 
arthritic  attacks,  or  gouty  asthma  may  occur  in 
early  life  and,  later,  articular  gout  may  develop, 
or  gouty  asthma  may  be  the  only  form  of  gout 
inherited  irom  a  parent  who  was  the  subject  of 
articular  gout. 

Gouty  puZmonari/ congestion. — This  is  usually 
at  the  base  of  the  lungs,  but  occasionally  may  be 
apical.  It  is  accompanied  by  hsemoptysis,  and 
is  a  condition  that  may  be  mistaken  for  phthisis. 

IRREGULAR    GOUT   AFFECTING   THE   HEART   AND 
VESSELS. 

Cardiac  irritability. — Paroxysmal  attacks  ot 
cardiac  irritability  are  very  apt  to  occur  in  gouty 
subjects.  The  attacks  are  nervous  in  origin,  and 
are  evidenced  by  irregularity,  tachycardia,  or  oc- 
casionally bradycardia,  and  by  dyspnoea  if  organic 
disease  of  the  heart  exist. 

Anginal  and  pseudo- anginal  attacks. — These 
attacks  may  occur  either  in  connection  with  chronic 
gout,  or  as  an  occasional  manifestation  of  irregular 
gout.  For  a  description  of  the  associated  symptoms 
see  pp.  113,  215,  216. 

Gouty  iMehitis. — This  affection  is  a  fairly 
common  complication  of  chronic  gout,  but  it  may 
also  be  a  phase  of  irregular  gout.  It  may  occur 
either  in  the  veins  of  a  portion  of  a  limb  which 
is  the  seat  of  gouty  inflammation,  or  in  veins  quite 


Irregular  Gout.  119 

apart  from  the  presence  of  gouty  inflammation  in 
the  vicinity.  The  veins  of  the  lower  extremities 
are  most  commonly  affected,  especially  the  veins  of 
the  calf  This  affection  is  not  uncommonly  of 
prolonged  duration,  and  is  very  apt  to  recur.  In 
consequence  of  the  thrombosis  that  ensues  great 
care  must  be  exercised  to  prevent  detachment  of 
the  clot,  and  the  consequent  risk  of  pulmonary 
embolism.  The  oedema  of  the  limb  consequent 
on  the  thrombosis  generally  persists  for  some 
time. 

IRREGULAR   GOUT   AFFECTING  THE   NERVOUS 
SYSTEM. 

Migraine  and  neuralgia. — Attacks  of  migraine 
and  of  neuralgia  not  unfrequently  occur  in  persoES 
of  gouty  habit,  and  are  in  certain  cases  dependent 
on  the  gouty  condition.  The  commonest  form  of 
gouty  neuralgia  is  sciatica,  the  next  commonest  is 
facial  neuralgia. 

Neuritis. — Peripheral  neuritis  of  gouty  origin 
occasionally  occurs.  Gouty  neuritis  or  perineuritis 
may  occur ;  the  symptoms  are  numbness,  tingling, 
loss  of  power  in  the  affected  part,  muscular  wasting 
occasionally,  and  sometimes  very  severe  pain.  The 
sciatic  nerve  and  the  brachial  plexus  and  its 
branches  are  most  liable  to  this  form  of  perineuritis 
or  neuritis.  The  affection  is  probably  started  by 
a  deposit  of  sodium  biurate  in  the  nerve-sheath 
setting  up  a  perineuritis,  with  subsequent  effusion 
of  lymph  within  the  sher.th,  and  consequent  com- 
pression of  the   nerve   fibres.     When   this   occurs 


120         The   Various  Forms  of  Gout. 

in  the  sciatic  nerve  it  is  the  cause  of  the  severe 
and  prolonged  sciatica  that  some  gouty  subjects 
suffer  from. 

Inf),so7)inia  is  an  occasional  accompaniment  or 
manifestation  of  irregular  gout.  This  condition 
may  be  due  to  the  ingestion  of  improper  food, 
giving  rise  to  abnormal  gastric  fermentation,  or  to 
hepatic  derangement.  In  such  cases  it  is  fre- 
quently accompanied  by  heartburn  and  palpitation. 

Mental  depression  is  frequently  associated  with 
gouty  attacks  affecting  the  liver,  and,  as  a  rule, 
is  almost  immediately  relieved  by  a  dose  of  blue 
pill  at  night,  followed  by  a  purge  of  Epsom  salts  in 
the  morning. 

Attacks  of  vertigo  and  epilepsy  are  occasionally 
associated  with  the  gouty  state.  Gouty  inflamma- 
tion of  the  meninges  of  the  spinal  cord  occasional!}' 
occurs,  associated  Avith  pain  and  tenderness  over 
the  affected  area,  and  with  pain  and  hyperiesthesia 
in  the  lower  extremities.  Three  cases  of  transient 
paraplegia  supposed  to  have  been  due  to  gouty 
congestion  of  the  spinal  cord  have  been  described. 

IRllEGULAR   GOUT   AFFECTIXG    THE   GEXITO-URIX.\RY 

SYSTEM. 

Gouty  kidney. — As  previously  stated  (see  pp. 
60 — 63),  I  hold  the  view  that  a  functional  affection 
of  the  kidneys,  interfering  with  the  proper  elimina- 
tion of  uric  acid,  is  the  primary  factor  in  the  pro- 
duction of  gout.  This  functional  affection  may 
subside  if  the  exciting  cause  of  it  be  removed,  or 
it  may  pass  on  to  a  structural  lesion,  which  is  then 


Irregular  Gout.  121 

of  the  contracted  granular  type.  The  symptoms 
associated  with  the  gouty  kidney  so  produced  are 
those  usually  met  with  in  cases  of  contracted 
granular  kidney.  There  is  increased  frequency  of 
micturition,  and  more  than  the  normal  quantity  of 
urine  is  passed.  The  urine  may  or  may  not  con- 
tain a  small  quantity  of  albumen.  The  arterial 
tension  is  increased,  and  this  constitutes  a  point  of 
great  importance  to  be  noticed,  since  cerebral 
haemorrhage,  hypertrophy  and  dilatation  of  the 
heart,  and  cons^estion  of  the  luno-s  are  liable  to 
supervene  on  this  condition. 

JJ'vic  acid  gravel  and  calculi. — These  deposits 
frequently  occur  in  early  life  among  those  with  a 
gouty  inheritance,  and  are  not  uncommonly  fol- 
lowed later  in  life  by  true  gouty  attacks.  The  pres- 
ence of  uratic  deposits  in  the  kidney  may  produce 
a  referred  pain  down  the  back  and  sometimes  the 
front  of  the  thigh.  This  pain  may  be  sufficiently 
severe  to  interfere  with  walking,  and  is  apt  to  be 
confounded  with  sciatica  or  rheumatism.  The  pain 
is  a  referred  one  and  is  dependent  on  the  irritation 
produced  within  the  kidneys,  which  irritation  is 
caused  by  uratic  deposits,  or  by  the  passage  of  fine 
uric-acid  gravel,  or  occasionally  by  the  passage  of 
an  excessive  amount  of  uric  acid,  as  sometimes 
occurs  in  cases  of  gouty  diabetes.  A  careful  ex- 
amination of  the  urine  and  palpation  of  the  kidneys 
wdll  reveal  the  source  of  such  referred  pains. 

Irritahility  of  the  bladder  is  associated  wdth 
the  passage  of  scanty  urine  of  high  specific  gravity, 
which    3^ields    a    copious    deposit    of    amorjDhous 


122  The   Various  Forms  of  Gout. 

urates  on  cooling.  Gouty  cystitis,  urethritis, 
orchitis,  ovaritis,  and  metritis  have  been  described, 
but  it  is  doubtful  whether  they  are  true  gouty 
affections. 

IRREGULAR  GOUT   AFFECTING   THE   SKIN. 

Gouty  subjects  are  peculiarly  liable  to  certain 
affections  of  the  skin,  and  amongst  those  who  have 
inherited  a  gouty  tendency  the  skin  affections  may 
constitute  the  only  manifestation  of  gout.  It  is 
doubtful  whether  these  skin  affections  are  ever  due 
to  the  direct  irritant  effect  of  either  sodium  quad- 
riurate  or  biurate  contained  in  the  sweat.  They 
are  more  probably  nervous  in  their  origin.  The 
following  are  the  skin  affections  liable  to  be 
associated  with  the  gouty  state. 

Eczema. — This  disease  of  the  skin  more  fre- 
quently occurs  in  association  with  gout  than  any 
other.  It  frequently  precedes  arthritic  gout,  and 
may  even  occasionally  be  the  sole  manifestation  of 
gout.  It  may  assume  either  the  acute  or  chronic 
form,  and  generally  occurs  symmetrically  on  both 
sides  of  the  body.  It  is  most  prone  to  occur  in 
spring,  and  is  very  apt  to  recur.  Gouty  eczema 
occurs  most  frequently  in  the  following  situations : 
the  external  ear  and  around  it,  the  face  and  fore- 
head, the  back  of  the  neck,  the  flexures  of  the 
joints,  the  scrotum  and  prepuce,  the  backs  of  the 
hands  and  feet,  the  interdigital  surfaces,  and  more 
rarely  on  the  arms,  legs,  and  trunk. 

Herpes  is  not  unfrequently  met  with  in  associ- 
ation with  gout. 


Irregular  Gout.  123 

Pruritus  and  pr-w-Wf/o  occasionally  occur  in 
gouty  subjects,  especially  in  connection  with  gouty 
glycosuria.  Pruritus  is  generally  localised,  and 
especially  affects  the  arms  and  the  vulva;  occa- 
sionally it  is  general. 

Urticaria  sometimes  occurs  as  a  result  of  the 
gouty  state.  Psoriasis,  acne,  boils,  and  carbuncles 
have  been  stated  to  be  occasionally  associated  with 
gout.  The  nails  of  gouty  subjects  tend  to  become 
thin  and  brittle,  and  usually  present  a  longitudinal 
striation,  producing  the  condition  known  as  "  the 
reedy  nail." 

OTHER  IRREGULAR  GOUT  AFFECTIONS. 

Glycosuria  and  diabetes. — The  development  of 
glycosuria  or  diabetes  in  persons  of  gouty  ancestry 
is  undoubted.  The  glycosuria  is  in  all  probability 
frequently  hepatic  in  its  origin.  Glycosuria  is 
generally  associated  with  some  form  of  irregular 
gout,  and  but  seldom  with  the  ordinary  articular 
gout,  but  very  occasionally  it  alternates  with  true 
gouty  attacks,  and  then,  while  the  glycosuria  lasts 
the  patient  is  quite  free  from  articular  gout,  audi  vice 
versa.  The  glycosuria  may  at  first  be  very  slight, 
but  if  not  checked  by  proper  dietetic  treatment  it 
may  lapse  into  true  diabetes.  With  regard  to  the 
prognosis  in  gouty  diabetes,  much  depends  on  the 
manner  in  which  the  affection  responds  to  dietetic 
treatment.  If  the  sugar  in  the  urine  quickly  dis- 
appear, and  if  several  months  elapse  before  its  re- 
appearance, then  the  prognosis  is  fairly  good,  and 
life  may  continue  for  many  years. 


124  The   Various  Forms  of  Gout. 

Hepatic  congestion. — A  condition  of  congestion 
of  the  liver,  or  possibly  of  subacute  parenchymatous 
hepatitis,  popularly  known  as  "  gout  in  the  liver,"  is 
occasionally  met  with  in  gouty  subjects,  or  in  those 
who  have  inherited  a  gouty  tendency. 

Gouty  affections  of  the  eye.— A.  gouty  inflamma- 
tion of  any  of  the  structures  of  the  eye  may  occur. 
Conjunctivitis  and  iritis  are  the  two  commonest 
83^6  affections  caused  by  the  gouty  condition. 

Deafness. — Occasionally  a  gouty  neuritis  affect- 
ing the  terminations  of  the  auditory  nerve  causes 
deafness. 

RETROCEDENT   OR   METASTATIC   GOUT. 

This  form  of  gout  occurs  when  a  sudden  sub- 
sidence of  the  inflammation  in  a  gouty  joint  is 
succeeded  by  the  development  of  the  disease  in 
one  or  more  of  the  internal  viscera,  such  as  the 
stomach,  intestines,  heart,  or  liver.  Persons  subject 
to  retrocedent  gout  are  generally  in  a  debilitated 
condition,  and  of  feeble  constitution.  The  attacks 
frequently  follow  an  exposure  to  cold  while  suffering 
from  an  articular  attack,  and  especially  after  in- 
discretion in  diet.  Attacks  of  retrocedent  gout 
have  also  not  uncommonly  followed  the  extremely 
baneful  practice  of  suddenly  plunging  a  gouty  foot 
into  cold  water.  If  the  attacks  rapidly  shift  their 
position  the  affection  is  termed  flying  gout.  It  is 
quite  possible  that  attacks  of  retrocedent  gout  are 
caused  by  a  deposition  of  the  crystalline  sodium 
biurate  in  the  affected  viscus,  and  that  this  crystal- 
line biurate  acts  as  a  mechanical  irritant,  and  so 


Retrocedent  Gout.  125 

produces  inflammation  of  the  organ.  On  the  other 
hand,  these  attacks  may  simply  be  of  nervous  reflex 
origin,  due  to  vaso-motor  disturbance  producing  a 
condition  of  hyper^emia  or  congestion  of  the  affected 
viscus.  The  following  are  the  principal  forms  of 
retrocedent  gout,  with  the  symptoms  indicative  of 
the  sudden  transference  of  the  attack  to  the 
affected  viscus. 

Retrocedent  gout  of  the  stoTnach. — The  symp- 
toms are  severe  pain  in  the  stomach,  accompanied 
usually  by  vomiting  and  a  feeling  of  general 
oppression,  depression,  and  faintness.  Palpitation 
may  occur. 

Retrocedent  gout  of  the  intestines. — The  usual 
symptoms  are  severe  abdominal  pain,  vomiting, 
tympanites,  and  constipation. 

Retrocedent  gout  of  the  heart. — The  symptoms 
are  severe  paljDitation,  pain  in  the  region  of  the 
heart,  a  sensation  of  constriction  of  the  chest, 
dyspnoea,  a  small  feeble  pulse,  and  great  anxiety. 
Syncopal  attacks  may  occur. 

Retrocedent  gout  of  the  brain. — Apoplexy  is  the 
most  frequent  symptom.  Congestion  of  the  brain 
or  meninges  may  occur,  and  may  be  followed  by 
headache,  stupor,  convulsions,  delirium,  and  occa- 
sionally by  maniacal  attacks.  Transient  attacks 
of  aphasia,  amnesia,  and  hemiplegia  sometimes 
occur,  and  are  probably  due  to  congestion  of  the 
brain. 

Gouty  orchitis  and  parotitis  of  meta- 
static origin  have  occasionally  been  know^n  to 
occur. 


126  The  Diagnosis  of  Gout. 

diagnosis  and  progxosis. 

The  diagnosis  of  an  attack  of  acute  gout  as  a 
rule  presents  no  difficulty  (see  pp.  107,108).  In  its  sub- 
acute and  chronic  forms  gout  must  be  distinguished 
from  rheumatism,  rheumatoid  arthritis,  and  from 
synovitis  of  traumatic,  pyaemic,  or  gonorrhoea! 
origin.  The  appearance  of  the  joint  (see  p.  108), 
the  discovery  of  tophi,  and  the  family  history  are 
the  main  pomts  on  which  to  rely. 

Distinction  of  gout  from  rheumatism. — The 
sweating  in  acute  rheumatism  is  much  more 
copious  than  in  acute  gout.  Rheumatism  especially 
attacks  the  larger  joints,  whereas  gout  attacks  the 
smaller  joints  most  frequently,  wdth  the  exception 
of  the  knees.  The  oedema  around  the  gouty  joint 
and  the  pitting  on  pressure  are  characteristic  and 
of  great  assistance  in  distinguishing  the  affection 
from  rheumatism.  In  gout  desquamation  of  the 
cuticle  of  the  affected  joint  occurs  later,  but  not 
in  cases  of  rheumatism.  In  connection  with 
attacks  of  gout  in  the  larger  joints,  such  as  the 
great  toe  and  knee  joints,  inflammation  of  the  con- 
tiguous lymphatic  vessels  occasionally  occurs,  and 
the  glands  in  the  neighbourhood  of  the  affected 
part  are  usually  enlarged  and  tender  on  pressure. 
As  previously  mentioned,  the  discovery  of  tophi 
and  the  family  history  are  of  immense  service  in 
distinguishing  gout  from  rheumatism. 

Distinction  of  gout  from  rheumatoid  arthritis. 
— The  severity  of  the  pain  generally  serves  to  dis- 
tinguish gout,  there  being  no  very  acute  pain  in 


Prognosis  of  Gout.  127 

the  affected  joints  of  rheumatoid  arthritis.  More- 
over, in  connection  with  rheumatoid  arthritis  there 
is  a  history  of  the  different  joints  being  affected  at 
different  times,  but  without  the  invasion  of  a  new 
joint  being  accompanied  by  amehoration  of  those 
previously  affected,  and  the  history  of  the  disease 
shows  a  continuity  in  the  affection  of  the  joints, 
instead  of  a  periodicity  as  in  gout.  Chronic  gout 
of  the  hands  may  be  distinguished  from  rheumatoid 
arthritis  by  the  greater  symmetry  that  is  generally 
displayed  in  the  finger  joints  of  the  two  hands  in 
.  connection  with  the  last-mentioned  disease. 

Prognosis. — If  no  complications  arise,  if  the 
attacks  are  not  too  frequent,  and  if  no  serious 
amount  of  albuminuria  occurs,  the  disease  is  not 
likely  materially  to  shorten  life,  especially  if  the 
patient  is  amenable  to  proper  treatment  and 
discipline.  Moreover,  although  gout  has  generally 
been  regarded  as  a  more  or  less  incurable  disease, 
the  view  as  to  its  renal  origin  renders  the  possibility 
of  cure  much  more  reasonable. 


128 


\^m  III. 


THE  AUTHOR'S  INVESTIGATIONS  OF  CER- 
TAIN POINTS  CONNECTED  WITH  THE 
TREATMENT  OF  GOUT. 

CHAPTER  X. 

Experimental  investigation   of  certain    conditions    and 
factors  affecting  the  solubility  and  the  precipitation 
of  sodium  quadriurate  and  sodium  hiurate. 

THE   ALKALINITY   OF   THE   BLOOD   IX   HEALTH   AND 

IN    GOUT. 

It  is  well  known  that  an  attack  of  gout  may 
be  accelerated  by  ingestion  of  food  or  beverages 
harmful  either  as  regards  their  quality  or  quantity. 
Such  substances  may  exert  a  direct  or  indirect 
chemical  action  which  facilitates  the  precipitation 
of  sodium  biurate — this  is  the  chemical  view — 
or  they  may  possibly  exert  a  physical  action  only 
in  hastening  such  precipitation  —  this  is  the 
mechanical  view.  A  view  which  has  previously 
been  referred  to,  and  which  is  commonly  held  as 
to  the  influence  of  diet  and  certain  beverages  in 
accelerating  an  attack  of  gout,  is  that  such  sub- 
stances reduce  the  alkalinity  of  the  blood  and  so 
hasten  the  precipitation  of  sodium  biurate.  It  is 
remarkable  what  a  number  of  writers  incline  to  the 
view  that  diminution  of  the  alkalinity  of  the  blood 


Alkalixity  of  the  Blood.  129 

cai.ises  tlie  deposition  from  it  of  sodium  biuratc, 
and  that  a  subsequent  rise  in  alkalinity  causes 
solution  of  the  previously  formed  deposits.  It  is 
assumed  that  a  nitroQfenous  animal  diet  diminishes 
the  alkalinity  of  the  blood  and  so  causes  deposition 
of  sodium  biurate.  It  is  also  assumed  that  a 
similar  result  is  caused  by  the  acids  contained  in 
wines  and  beers ;  and  that  the  pains  in  the  joints, 
that  frequently  occur  in  gouty  subjects  soon  after 
taking  certain  wines  or  beers,  are  due  to  deposition 
of  biurate  following  on  the  reduction  of  the  alka- 
linity of  the  blood  by  the  acid  so  introduced. 
Now,  in  the  first  place,  is  there  any  substantial 
proof  that  the  alkalinity  of  the  blood  is  much  re- 
duced in  connection  with  gout  ?  Careful  experi- 
ments, conducted  by  Klemperer,"^  show  that  the 
alkalinity  of  the  blood  of  gout  is  but  very  little,  if 
at  all,  diminished,  and  that  corresponding  varia- 
tions in  the  alkalinity  may  frequently  be  met  with 
in  healthy  individuals.  In  the  following  table 
(Table  Y.)  are  shown  the  results  of  the  determina- 
tions that  I  made  of  the  alkalinity  of  the  blood  f 
of  a  patient  suffering  from  subacute  gout ;  the 
estimations  were  made  mostly  on  alternate  days, 
throuo^hout  the  duration  of  the  attack.  The  nor- 
nial  alkalinity  of  healthy  blood  is  shown  for  com- 
parison at  the   foot   of  the  table.      This   normal, 

*  Deutsche  medicinische  Wochenschrift,  1895,  xxi.,  p.  6o5. 

f  The  process  employed  for  determining  the  alkalinity  of  the 
blood  was  the  one  recently  devised  and  dtscribed  by  Dr.  A.  E. 
Wright  [The  Lancet^  Sept.  ISlh,  1897).  This  process  is  an  ex- 
tremely ingenious  and  reliable  one,  and  possesses  the  great 
advantage  of  not  requiring  more  than  two  or  three  drops  of  blood 
in  order  to  make  an  accurate  determination  of  the  alkalinity. 

J 


I30 


A  UTHOR  s  Investiga  tions. 


alkalinity  is  the  average  of  the  determinations  that 
I  made  of  the  alkalinity  of  the  blood  of  twenty-five 
healthy  male  adults. 

TABLE   V. 

Sltowlng   the   results   of  the  determination   of  the  alkalinity  of  the 
blood  of  an  adult  man  during  an  attack  of  subacute  gout. 


Dates  of  determinations,  and  relations  to  treatment. 

Alkalinity  represented 
as  percentage  of  an- 
liydrous  sodium  car- 
bonate jn'esent  in  the 
blood. 

Feb. 

4th  (commencement  of  attack,  and  be- 

fore treatment  was  begun) 

0-167 

6th\ 

0-167 

8th 

0167 

j> 

r^th  '      (Treated  with  colchicum  only) 

0-156 
0167 

j> 

loth 

0-158 

17thj 

0-158 

19th  \ 

0167 

)> 

22nd 

(Treated  with  citrate  of  potas- 

0-180 

24  th 

sium  and  iodide  of  potassium 

0-173 

•5 

26th 
28th 

only) 

0161 
0179 

.Mar 

.2nd           

0  167 

Average  alkalinity  throughout  the  attack  ... 

0  166 

Alkalinity  of  normal  blood    ... 

{Average  of  the  determinations  of  the  alkali)iitg 

of  the    blood   of    tiventy-Jire    healthy    male 

adults.) 


0-10< 


The  alkalinity  of  healthy  blood  varied  from 
0161  to  0185,  the  average  being  0167,  and  it  is 
seen  in  the  table  that  the  alkalinity  of  the 
gouty  blood  varied  from  0156  to  0180,  the 
average  being  01 60,  which  is  practically  the  same 
as  the  normal  alkalinity.  These  results  show  that 
in  this  case  of  subacute  gout  the  variations  in  the 


Alkalixity  of  the  Blood.  131 

alkalinity  of  the  blood  were  not  greater  than  those 
met  with  in  healthy  individuals.  There  is  certainly 
no  good  ground  for  the  belief  that  an  "  acid 
dyscrasia  "  underlies  the  gouty  condition.  Recent 
researches  show  that  a  diminution  of  the  alkalinity 
of  the  blood  is  a  common  pathological  condition 
in  diseases  that  are  in  no  way  associated  with  uratic 
precipitation,  such  as  acute  rheumatism,  leukaemia 
diabetes,  carcinoma  and  pyrexia.  In  the  second 
place,  I  have  been  unable  to  meet  with  any  experi- 
mental proof  that  a  diminution  in  the  alkalinity  ot 
blood,  containing  uric  acid  in  solution,  either 
facilitates  the  deposition  of  sodium  biurate  from  it, 
or  diminishes  its  solvent  power  for  sodium  biurate 
or  for  uric  acid.  I  therefore  considered  it  advis- 
able experimentally  to  investigate  these  different 
points,  and  for  that  purpose  the  following  series  of 
experiments  were  undertaken. 

EXPERIMENTS  SHOWING  TO  WHAT  EXTENT  THE  RATE 
OF  FORMATION  AND  PRECIPITATION  OF  SODIUM 
BIURATE  IS  EFFECTED  BY  DIMINISHING,  BY 
THE  ADDITION  OF  ACIDS,  THE  ALKALINITY  OF 
BLOOD   SERUM   CHARGED   AVITH   URIC   ACID. 

Seven  bottles,  each  containing  40  c.c.  of  blood 
serum,  were  raised  to  100°  F.,  and  then  charged 
with  uric  acid  to  the  extent  of  1  in  1,000. 
As  soon  as  the  uric  acid  was  dissolved,  varyino- 
quantities  of  hydrochloric  acid  were  added  to  the 
contents  of  three  of  the  bottles,  and  of  tartaric  acid 
to   another   three,  so   as   partially   to  reduce   the 


n2 


A  uTHOR  's  In  ves  tig  a  tions. 


alkalinity  of  the.serum  ;  the  contents  of  the  seventh 
bottle  Avere  left  unaltered.  The  bottles  were  kept 
in  a  warm  chamber  at  100°  F.,  and  the  commence- 
ment of  the  precipitation  of  sodium  biurate  crystals 
was  then  looked  for  by  examining  some  of  the 
contents  of  the  bottles  under  the  microscope  every 
few  minutes,  so  as  to  note  the  time  when  the 
formation  of  biurate  crystals  commenced.  The 
quantities  of  hydrochloric  acid  added  to  the  con- 
tents of  three  of  the  bottles  were  such  as  to 
neutralise  respectively  three-fourths,  one-half,  and 
one-fourth  of  the  alkalinity  of  the  serum  remaining 
after  solution  of  the  uric  acid.  To  the  other  three 
bottles  corresponding  quantities  of  tartaric  acid 
were  added  to  produce  similar  results.  The  follow- 
ing tables  (Table  VI.  and  Table  VII.)  show  the 
results  of  these  experiments. 

TABLE   VI. 

The  results  of  experiments  made  with  Hood  scrum  charged  uith  uric 
acid,  to  show  the  effect  which  the  diminution  of  the  alkalinity  of 
the  serum,  by  the  addition  of  hydrochloric  acid,  has  on  the  pre- 
cipitation of  sodium  biurate. 


Si)lutioii. 


Blood  Eerum  containing   I  in 
1,000  uric  acid. 

The  same  one-fourth  neutral- 
ised by  hydrochloric  acid. 

The  8ame  one-half  neutralised 
by  hydrochloric  acid. 

Tlie  same  three-fourths  neuti-al- 
ised  by  hydrochloric  acid. 


Coinineufcnieiit  of  jireciiatation. 


Crystals  of  sodium  biurate  first 
appeiired  in  6 — 7  hours. 

Do. 


Do. 


Some  crystals  of  uric  acid  ap- 
peared in  0  minutes.  Crystals 
of  todium  biurate  first  ap- 
peared in  12  hoxu'S. 


Experiments  with  Sodium  Bi urate,     133 

It  will  be  seen  from  the  results  of  these  experi- 
ments that  the  effect  of  diminishino^  the  alkalinity 
of  blood  serum  as  far  as  one-half  has  no  influence 
whatever  in  hastening  the  conversion  of  the  sodium 
quadriurate  into  biurate,  or,  in  other  words,  does 
not  influence  the  deposition  of  sodium  biurate  from 
the  serum.  When  the  alkalinity  is  reduced  by 
three-fourths,  by  the  addition  of  hydrochloric  acid, 
some  crystals  of  uric  acid  were  almost  immediately 
precipitated,  but  when  this  precipitation  of  uric 
acid  had  ceased,  then  the  deposition  of  sodium 
biurate  did  not  begin  till  twelve  hours  had  elapsed. 
The  reason  that  the  deposition  of  sodium  biurate 
was  delayed  a  longer  time  than  in  the  cases  of  the 
serum,  the  alkalinity  of  which  was  reduced  respec- 
tively by  one-fourth  and  one-half,  was  that  the 
removal  of  some  of  the  uric  acid  rendered  the 
solution  of  sodium  quadriurate  weaker,  and,  as  has 
been  pointed  out  by  Sir  William  Roberts,  the 
amount  of  uric  acid  in  solution  exercises  a  very 
important  influence  on  the  rate  of  maturation  of 
the  quadriurate,  and  the  advent  of  precipitation  of 
the  biurate.  This  early  shower  of  uric  acid  crystals 
that  occurred  when  sufficient  hydrochloric  acid  was 
added  to  the  blood  serum  to  neutralise  three-fourths 
of  its  alkahnity  has  no  bearing  whatever  on  the 
chemistry  of  the  gouty  attack,  since  the  gouty 
deposit  always  consists  of  sodium  biurate,  and  never 
of  uric  acid.  The  following  table  shows  the  results 
of  the  experiments  obtained  with  blood  serum,  the 
alkalinity  of  which  was  partially  reduced  by  means 
of  tartaric  acid 


134  Author's  Investigations. 

TABLE  Yir. 

The  results  of  experiments  made  ivith  blood  serum,  charged  tvith  uric 
acid,  to  show  the  effect  which  the  diminution  of  the  alkalinity  of 
the  serum,  by  the  addition  of  tartaric  acid,  has  on  the  precipita- 
tion of  sodium  biurate. 


Solution. 

Commencement  of  precipitation. 

Blood   serum   containing-  1   in 
1,000  uric  acid. 

Crystals  of  sodium  biurate  first 
appeared  in  6 — 7  hours. 

The  same,  one-fourth  neutral- 
ised by  tartaric  acid. 

Do. 

The  same,  one-half  neutralised 
hy  tartaric  acid. 

Do. 

The  same  three-fourths    neu- 
tralised by  tartaric  acid. 

Do. 

From  these  experiments  it  is  evident  that  even 
the  reduction  of  the  alkahnitj  of  blood  serum  by 
three-fourths  has  no  influence  in  hastening  the 
precipitation  of  sodium  biurate  from  blood  serum 
impregnated  with  uric  acid.  The  view,  therefore, 
that  a  diminution  of  the  alkalinit}^  of  the  blood 
promotes  an  attack  of  gout  by  favouring  the  depo- 
sition of  sodium  biurate  is,  in  my  opinion,  untenable. 
In  order  to  s^ive  an  idea  of  the  amount  of  acid  that 
would  be  required  to  reduce  the  alkalinity  of  the 
blood  of  an  adult  human  being  by  three-fourths,  I 
made  the  following  estimation  and  calculation.  I 
found  that  the  acidity  of  some  1847  port,  reckoned 
as  tartaric  acid,  was  equal  to  six  grains  of  acid  to 
the  wineglassful.  In  order  to  neutralise  three- 
fourths  of  the  alkalinity  of  the  blood  serum  of  a 
man  of  average  weight,  it  would  be  necessary  that 
all  the  acid  contained  in  two  bottles  of  such  port 


Experiments  with  Uric  Acid.         135 

should   be   introduced   at   one    moment   into   the 
circulation. 

EXPERIMENTS  TO  SHOW  THE  SOLVENCY  OF  URIC 
ACID  IN  BLOOD  SERUM,  THE  ALKALINITY  OF 
WHICH  HAS  BEEN  REDUCED  BY  THE  ADDITION 
OF    AN   ACID. 

The  effect  of  hydrochloric  and  tartaric  acids  re- 
sjDectively  Avas  investigated.  As  will  be  seen  from 
the  results,  there  is  a  remarkable  difference  in  the 
solvent  power  of  partially  neutralised  blood  serum 
for  uric  acid,  accordingly  as  its  alkalinity  is  reduced 
by  the  addition  of  hydrochloric  or  tartaric  acid. 
The  experiments  were  carried  out  in  the  following 
manner : — Four  bottles  containing  25  c  c.  each  of 
blood  serum  were  taken;  three  of  them  were 
treated  respectively  with  different  quantities  of 
hydrochloric  acid,  so  as  to  reduce  the  alkalinity  of 
the  serum  in  one  case  by  one-fourth,  in  the  second 
case  by  one-half,  and  in  the  third  case  by  three- 
fourths  ;  the  contents  of  the  remaining  bottle  were 
left  untouched.  The  bottles  were  placed  in  the 
warm  chamber  till  their  contents  were  at  100^  F., 
and  then  an  excess  (60 — 70  milligrammes)  of  uric 
acid  was  added  to  each.  They  were  kept  in  the 
warm  chamber  for  two  hours,  during  which  time 
they  were  frequently  agitated ;  the  contents  of  the 
bottles  were  then  filtered  from  undissolved  uric 
acid,  and  the  dissolved  uric  acid  in  each  filtrate 
was  estimated.  The  following  table  shows  the 
results. 


136 


A  uthor's  Ixvestiga  tions. 


TABLE  VI 11. 

SJiouing  the  solnhUittj  of  uric  acid  at  100°  F.  in  tmaltered  blood 
serum  and  in  blood  serum  the-  alkalinity  of  which  is  proportion- 
attly  reduced  by  the  addition  of  hijdroohloric  acid. 


Scilvtnit. 


Unaltered  serum 

>Serum   one-fourth   neutralised    by   hydro- 
chloric acid  .. . 

Serum     one-half     neutralised    hy     hydro- 
chloric acid ... 

Serum  three-fourths  neutralised  hy  hydro- 
chloric acid... 


Uric  afiil  dissolved. 


2-03  per  1,000 
148         „ 
1-00         „ 
0  45 


Similar  pxperiments  were  carried  out  using  tartaric 
acid  in  the  place  of  hydrochloric  acid.  The  follow- 
ing table  shows  the  results. 

TABLE   IX. 

Showing  the  solubility  of  uric  acid  at  100°  F.  in  unaltered  blood 
sei-ntn  and  in  blood  strwn  the  alkalinity  of  which  is  proportion- 
ately reduced  by  the  addition  of  tartaric  acid. 


SolY.nt. 


Unaltered  serum 


Serum   one-fourth   neutralised  by  tartaric 
acid  ...         ...         


Uric  acid  dissolved. 


2-03  per  1,000. 


201 


Serum  one-half  neutralised  by  tartaric  acid  201 

202 


Seium  three-fourths  neutralised  by  tartaric 
acid 


It  is  seen  from  the  results  of  these  experiments 
that  if  the  alkalinity  of  blood  serum  is  reduced  by 
the  addition  of  hydrochloric  acid,  the  solvency  of 
the  serum  for  uric  acid  is  correspondingly  altered. 


Experiments  with  Uric  Acid.         137 

This  is  what  would  be  expected,  since  the  conver- 
sion of  some  of  the  sodium  bicarbonate  of  the 
serum  into  sodium  chloride  renders  that  portion  of 
the  sodium  unattainable  by  the  uric  acid,  and 
prevents  the  solution  of  a  corresponding  amount  of 
the  latter  as  sodium  quadriurate.  Such  a  result, 
however,  does  not  follow  the  reduction  of  the 
alkalinity  of  the  serum  by  the  addition  of  an 
organic  acid,  such  as  tartaric  acid.  It  will  be  seen 
that  serum,  the  alkalinity  of  which  is  reduced 
respectively  by  one-fourth,  one-half,  and  three- 
fourths,  practically  does  not  vary  at  all  as  regards 
its  solvency  for  uric  acid.  The  explanation,  no 
doubt,  is  that  the  uric  acid  is  able  to  displace  the 
tartaric  acid  from  its  combination  with  sodium, 
and  utilise  the  sodium  of  the  tartrate  as  readily  as 
the  sodium  of  the  bicarbonate  to  form  the  soluble 
sodium  quadriurate.  Since  the  acidity  of  wines  is 
due  to  organic  acids  (mainly  tartaric,  mahc,  and 
succinic  acids),  it  would  seem  very  doubtful,  judg- 
ing from  the  results  of  these  experiments,  whether, 
even  if  any  alteration  in  the  allialinity  of  the  blood 
were  produced  by  the  drinking  of  acid  wines,  the 
solubility  of  uric  acid  in  such  blood  could  be 
affected  m  the  shghtest  degree. 

EXPERIMENTS  TO  SHOW  THE  SOLVENCY  OF  SODIUM 
BILTRATE  IN  BLOOD  SERUM,  THE  ALKALINITY 
OF  ^VHICH  HAS  BEEN  REDUCED  BY  THE  ADDI- 
TION  OF  AN   ACID. 

The  effect  of  hydrochloric   and  tartaric  acids 
respectively  was  investigated.      The  experiments 


138 


A  UTHOR  '5  In  ves  tig  a  tions. 


were   carried   out  in  a   similar   manner    to    those 

just  described,  except   that   an  excess  of  sodium 

biurate  was  substituted  for  the  uric  acid,  and  the 

disrestion   with   the   sodium   biurate    was    carried 

on  at  100"^  F.  for  five  hours.     The  following  tables 

show  the  results  : — 

TABLE    X. 

Shouing  the  .solabillti/  of  sodium  biurate  at  100°  i^.  in  unaltered  blood 
serum,  and  in  blood  serum  the  alkalinity  of  which  is  proportion- 

aiehj  reduced  b;/  the  addition  of  hydrochloric  acid. 


Solvent. 


Unaltered  serum 

Serum   one-fourth   neutralised    by   hydro- 
chloric acid ... 

Serum  one-half  neutralised  by  hydrochloric 
acid 

Serum  three-fourths  neutralised  by  hydro- 
chloric acid  ... 


Sodium  biurate 
dissolved. 


0-05  per  1,000 
0-05         „ 
0-07 
0-10 


These  results  show  that  sodium  biurate  is 
slightly  more  soluble  in  serum  which  has  been 
partially  neutralised  by  the  addition  of  hydro- 
chloric acid  than  it  is  in  unaltered  serum. 

TABLE   XI. 
Showing   the  solubility  of  sodium  biiirate  at    100'  F.    in    unaltered 
blood  serti-n,  and  in  blood  serum  the  alkalinity  of  tchich  is  pro- 
portionately reduced  by  the  addition  of  tartaric  acid. 


Solvent. 

Sodium  biurate 
dissolved. 

Unaltered  serum        

005  per  1,000 

Serum  one-fourth  neutralised  by  tartaric 
acid 

0-08         „ 

Serum  one-half  neutralised  by  tartaric  acid 

0-08 

Serum   three-fourths    neutralised    by   tar- 
taric acid     

0-12 

Experiments  with  Sodium  Bi urate.     139 

These   results  also   show  that  sodium  biurate 
is  more  soluble  in  serum  the  alkalinity  of  which 
has  been  reduced  by  the  addition  of  tartaric  acid 
than  it  is  in  unaltered  serum.     I  think   that  the 
view  that  uric  acid  is  deposited  in  the  liver,  spleen, 
joints,   and   fibrous    tissues   owing    to   diminished 
alkalinity  of  the  blood  should  be  abandoned.     It 
is  based  on  an  error — viz.,  that  the  deposit  is  uric 
acid,    whereas  it  is   sodium  biurate.     The  results 
of  the  experiments  that  have  just  been  described 
indicate   that  diminution  of  the  alkalinity  of  the 
medium  does  not  promote  the  deposition  of  sodium 
biurate.     The  other  view,  that  increased  alkalinity 
of  the  blood  dissolves  and  sweeps  out  the  accuinu- 
lations  of  uric  acid  from  the  various  organs  and 
tissues,  should  also,  in  my  opinion,  be  abandoned. 
It  is  based  on  the  same  error — viz.,  that  the  deposit 
is  uric  acid,  whereas  it  is   sodium  biurate.    That 
this  body  is  not  more  soluble  in  highly  alkaline 
fluids   has   been   proved    by    the    experiments   of 
Sir   AVilliam  Roberts,^    and  is  confirmed  by  the 
experiments  that  have  just  been  described.  Another 
erroneous  idea  in  my   opinion   is   that   uric    acid 
may  be  precipitated  from  the  blood  in  the  form 
of  insoluble  urates  by  certain  metallic  salts ;  these 
insoluble    urates    are    supposed    to   be   deposited 
in    various   tissues    or   organs,    and   yet   in   some 
mysterious  manner  to  be  subsequently  redissolved 
when  the  alkalinity  of  the  blood  rises.     There  is 
absolutely  no  experimental  proof  to  support  such 
a  statement. 

*  Crconian  Lectures  on  "  Uric- Acid  Gravel  and  Gout,"  1892. 


140 


CHAPTER    XL 

Experimental  investigation  of  the  influence  exerted  by 
the  mineral  constituents  of  meat,  tnilk,  and  vege- 
tables respectively  on  the  sohtbility  of  sodium 
biurate — The  influence  of  alcoholic  beverages  on  the 
gouty  process. 

INFLUENCE   OF   CERTAIN   ARTICLES  OF   DIET   ON    THE 
PRECIPITATION    OF    SODIUM   BIURATE. 

It  is  well  known  that  the  excessive  consumption 
of  rich  nitrogenous  food,  combined  with  excesses  in 
wine  and  malt  liquors,  both  induce  and  excite  gout. 
The  comparative  immunity  of  females  and  young 
people  from  gout  is  mainly  explained  by  the  absence 
of  such  determining  causes  of  the  gouty  attack, 
combined  Avith,  in  the  case  of  young  people,  the 
absence  of  predisposing  cause,  and  also  the  fact 
that  the  secreting  functions  are  in  full  activity. 
The  subjects  of  gout  are  generally  persons  who 
live  well  and  consume  a  large  amount  of  animal 
food.  Dr.  Budd,  speaking  from  a  long  and  ex- 
tensive professional  connection  with  a  large  rural 
district,  states  that  ho  never  knew  an  instance 
of  gout  occurring  among  agricultural  labourers. 

The  generally  accepted  view  that  a  highly 
nitrogenous  animal  diet  necessarily  produces  an 
excessive   amount   of    uric   acid   is   disproved   by 


Animal  and   Vegetable  Diets.         141 

the  experiments  of  Bleibtreu  and  of  Hirschfeld 
previously  referred  to.  Those  experiments  show 
that  there  is  an  increased  elimination  of  urea 
to  compensate  for  an  excessive  intake  of  nitro- 
genous food,  and  that  the  amount  of  uric  acid 
remains  practically  undiminished.  Judging  by 
the  results  of  the  experiments  which  have  been 
previously  described,  it  is  highly  improbable  that 
any  diminution  in  the  alkalinity  of  the  blood, 
which  might  be  produced  by  the  consumption 
of  an  excessive  amount  of  animal  food,  could  in 
any  way  affect  its  solvent  powers  for  uric  acid, 
or  accelerate  the  precipitation  of  sodium  biurate. 
My  own  view  is  that,  as  regards  the  production 
of  uric  acid  from  proteid  matter,  it  is  of  little 
importance  whether  the  proteid  is  of  animal  or 
vegetable  origin.  The  same  harm  may  result 
from  an  excessive  consumption  of  either  form 
of  proteid.  But  although  animal  and  vegetable 
proteids  may  react  alike  with  regard  to  the  pro- 
duction of  uric  acid,  it  is  quite  possible  that  the 
different  saline  constituents  of  animal  and  vege- 
table foods  might  very  materially  affect  the  solu- 
bility of  sodium  biurate  and  therefore  influence 
its  precipitation.  As  I  have  been  unable  to  find 
any  record  of  experimental  work  bearing  on  this 
matter,  I  thought  it  advisable  to  ascertain  if  the 
saline  substances  contained  in  different  articles  of 
diet  appreciably  affected  the  solvency  of  sodium 
biurate  at  the  temperature  of  the  human  body, 
as  obviously  the  subject  might  have  both 
a   pathological    and   therapeutical   bearing.      The 


142  Author's  Investigations. 

following     experiments     were     therefore     carried 
out. 

EXPERIMENTS  SHOWING  THE  INFLUENCE  OF  THE 
MINERAL  CONSTITUENTS  OF  MEAT,  MILK,  AND 
VEGETABLES  RESPECTIVELY  ON  THE  SOLUBILITY 
OF   SODIUM   BIURATE   AT    100'   F. 

A  series  of  experiments  were  undertaken, 
operating  upon  the  ash  respectively  of  lean 
beef,  milk,  and  mixed  vegetables  (potatoes, 
spinach,  and  French  beans).  The  experiments 
were  carried  out  in  the  following  manner: — The 
contents  of  a  number  of  bottles,  each  containins: 
100  c.c.  of  distilled  water,  were  mixed  with  known 
quantities  of  the  different  ashes  and  placed  in  the 
warm  chamber  until  their  contents  were  at  a 
temperature  of  100'  F.,  when  an  excess  of  sodium 
biurate  was  added  to  each.  The  bottles  were 
kept  at  100°  F.  for  five  hours,  during  which  period 
they  were  frequently  agitated.  At  the  end  of 
that  time  the  contents  of  the  bottles  Avere  filtered 
and  refiltered  through  double  filters  until  perfectly 
clear  filtrates  were  obtained.  The  amount  of 
uric  acid  in  each  of  the  filtrates  was  then  estimated 
by  adding  an  excess  of  strong  sulphuric  acid,  and 
titrating  with  the  standard  potassium  permanganate 
solution ;  the  quantity  of  uric  acid  found  was 
subsequently  calculated  into  terms  of  sodium 
biurate.  The  results  thus  obtained  are  shown 
m  the  following  tables.  The  solubility  of  sodium 
biurate  in  distilled  water  is  placed  at  the  head 
of  each  table  for  comparison. 


Experiments   with  Sodium  Bi urate.     143 

TABLE  XII. 

Showing  the  injlaencc  of  the  mijieral  constUuc/its  of  meat  {lean  beef) 
oil  the  solabllUi/  of  sodium  hluratc  at  100°/''. 


Mulveiit. 

yodium 
tlissD 

bi  unite 
Ived. 

Water 

MO  per  1,000 

Water  containing- :  — 

l-O  par 

oont.  of  moat  ash 

0-93 

0-5 
0-2 

55                           5) 

55                         55                                

0-76 
0-56 

O-l 

55                           55 

o:v2 

O-Oo 

5  '                           55                                  •  •  *                   •  •  •                   •  •  * 

0-15 

0-02 

55                           55 

0-11 

0-01 

55                           55 

0-85 

From  the  above  table  it  is  seen  that  the  mineral 
constituents  of  meat,  in  all  proportions  between 
10  and  001  per  cent,  diminish  the  solvency  of 
sodium  biurate.  The  effect  is  most  marked  Avhen 
the  proportions  are  between  01  and  0'02  per  cent., 
which  are  proportions  that  may  certainly  be  present 
in  the  blood  after  eatino^  a  few  ounces  of  meat. 
It  is  therefore  quite  possible  that  the  Avell-known 
influence  of  excessive  meat-eating  on  the  hastening 
or  maturing  of  an  attack  of  gout  may,  in  part 
at  least,  be  due  to  the  action  of  the  mineral  con- 
stituents of  the  meat. 

TABLE   XIII. 

Showing  the  influenee  of  the  mineral  constitacnts  of  milk  on  the 
soliihility  of  sodium  biurate  at  100°  F. 


Solvent. 

Sodium  1 
dissol 

.)iurate 
i'ed. 

Water  . 

•• 

Water  containing  : — 

1-10  per 

1,000 

rO  per 

cent 

.  of  millv  ash 

0-62 

55 

O-o 

5' 

0-58 

55 

0'2 

55                                 ••  • 

0-49 

>> 

0-1 

55 

0-44 

5> 

0-05 

55 

0-72 

55 

0-02 

55 

0-90 

55 

0-01 

55                                 •  •  •                   ••• 

0-94 

55 

144 


A  UTHOR  'S   I  A  VES  TIG  A  TIONS. 


From  the  foregoing  table  it  is  seen  that  the 
mineral  constituents  of  milk  in  all  proportions 
diminish  the  solvency  of  sodium  biurate.  The 
effect  is  most  marked  when  01  per  cent,  of  milk 
ash  is  present.  It  is  extremely  unlikely  that 
such  a  proportion  could  be  present  in  the  blood 
unless  a  person  were  exclusively  fed  for  some  time 
on  milk.  To  introduce  Ol  per  cent,  of  the  mineral 
constituents  of  milk  into  the  blood  would  require 
that  all  the  mineral  constituents  of  about  twenty- 
two  ounces  of  milk  should  be  introduced  at  one 
moment  into  the  blood  of  an  adult  of  average 
weight.  These  experiments  therefore  seem  to 
indicate  that  the  mineral  constituents  of  milk 
can  exercise  no  appreciable  influence  in  hastening 
or  maturing  an  attack  of  gout. 


TABLE   XIV. 

Showing  the  influence  of  the  mineral  constituents  of  vegetables 
(potatoes,  spinach,  and  beans)  on  the  soluhiiity  of  sodium  biurate 
at  100°  F. 


Sodium 

biurate 

Solvent. 

(iissu 

Ive.l. 

Water... 

110 

per  1,000 

Watei'  containinj.^  : — 

ro  per  cent. 

of 

vegetable  ash 

2- 1.5 

0-0 

»> 

1-70 

0-2 

>,                        

l-3o 

01 

,, 

1-1.5 

005 

,, 

110 

002 

,,                         ...          ... 

1-10 

001 

,, 

1-10 

From     Table     XIV.     it     is     seen     that     the 
mineral   constituents  of   vegetables   in   quantities 


Alcoholic  Beverages  and  Gout.       145 

of  01  per  cent,  and  above  very  appreciably  increase 
the  solvency  of  sodium  biurate.  In  quantities 
below  01  per  cent,  the  solutions  exercise  the  same 
solvent  power  on  the  biurate  as  distilled  water. 
These  experiments  indicate  that  the  mineral 
constituents  of  vegetables,  if  taken  in  sufficient 
quantities,  w^ould  delay  the  advent  of  an  attack 
of  gout  by  their  increasing  the  solvency  of  sodium 
biurate,  and  would  also  exert  a  solvent  effect  on 
gouty  deposits. 

INFLUENCE  OF  ALCOHOLIC  DRINKS  ON  THE 
GOUTY  PROCESS. 

It  is  well  known  that  certain  alcoholic  drinks 
injuriously  affect  the  gouty  process,  whilst  others 
exert  a  less  injurious  influence.  Alcoholic  drinks 
which  have  been  obtained  by  fermentation,  but 
which  have  not  been  submitted  to  distillation,  such 
as  wines  and  beers,  appear  to  exercise  a  more 
harmful  influence  than  if  the  same  amount  of 
alcohol  be  consumed  in  the  form  of  one  of  the 
distilled  spirits,  such  as  whisky,  brandy,  etc. 
Garrod  considers  that  the  reason  for  the  prevalence 
of  gout  in  the  south  of  England  and  its  rarity  in 
Scotland  is  chiefly  due  to  the  different  beverages 
drunk  in  the  two  countries. 

Distilled  spirits  contain  little  or  no  acid,  whilst 
wines  and  beers  are  distinctly  acid,  and  to  the 
acids  contained  in  these  drinks  many  physicians 
have  attributed,  and  still  do  attribute,  their  gout- 
inducing  properties.     The  acids  present  are  tartaric^ 

K 


T46 


A  UTHOR  '5  In  ves  tig  a  tions. 


succinic,  malic,  acetic,  formic,  propionic,  butyric 
and  oenanthic.  The  acidity  of  wines  is  mainly  due 
to  tartaric,  malic  and  succinic  acids.  The  amount 
of  free  acid  in  sound  wine,  reckoned  as  tartaric 
acid,  varies  between  0  3  and  0  7  per  cent.  I  found 
the  acidity  of  some  1847  port,  reckoned  as  tartaric 
acid,  to  be  0*6  per  cent.  Cider  owes  its  acidity 
mainly  to  malic  acid.  Its  total  acidity  is  usually 
01  per  cent.  If  we  arrange  the  various  wines  in 
(a)  their  order  of  acidity  and  (b)  the  order  of  their 
gout-inducing  power,  we  find  that  the  most  acid 
wines  are  not  those  which  most  predispose  to  gout. 
The  arrangement  of  wines  and  beers  in  the  order  of 
acidity,  beginning  with  the  most  acid,  is  that  given 
by  Dr.  Bence  Jones,  while  the  arrangement  in 
order  of  their  gout-inducing  power  is  that  given 
by  Sir  Alfred  Garrod  : — 


TABLE    XV. 

Wines  and  beers  arranged  in  order  of  acidity  and  go^it-inducing  power 


(«)  Acidity  (beginning  with  the 

(b)  Gout-inducing  power  (1 

leginning 

most  acid). 

with  the  must  powerful). 

Moselle 

Tort 

Bliine  wines 

Sherry 

Burgundy 

C)ther  stronger  wines 

Madeira 

Champagne 

Claret 

Stout  and  porter 

Champagne 

Strong  ales 

Port 

Claret 

Sherry 

Hock 

IM  alt  liquors 

Moselle 

Weaker  kinds  of  ; 

lies 

Claret,  hock,  moselle  and  the  weaker  kinds  of  ales 
have  comparatively  little  gout-inducing  power. 


Alcoholic  Beverages  and  Gout.       147 

gout-inducing  properties  of  certain  wines  and 
lieers  not  due  to  acids  or  sugar. 

Sir    Alfred   Garrod    considers   that   acidity   of 
alcoholic  liquors  cannot   have   much  influence  in 
determining  an  attack  of  gout,  as  port,  sherry  and 
malt   liquors,  which  are  the  most   powerful   pre- 
disposing agents,  are  amongst  the  least  acid,  whilst 
the   more   acid   wines,   such    as  clarets,  are   com- 
paratively harmless  in  this  respect.     This  opinion 
is  entirely  borne  out  by  the  experiments  I  have 
described,  which  show  that  a  diminution   of  the 
alkalinity  of  blood  serum  does  not  hasten  the  con- 
Version   of  sodium  quadriurate  into  biurate,  does 
not  diminish  the  solubility  of  sodium  biurate,  and 
therefore   cannot   promote    deposition   of    sodium 
biurate,  and  so  be  a  determining  cause  of  an  attack 
of  gout.     The  question  is — to  what  constituent  or 
constituents   of  wines   and   beers   are  their  gout- 
inducing  properties  due  ?     They  are  not  due  to  the 
alcohol  alone,  for  in  countries  such   as   Scotland, 
Norway,  Sweden,  and  Poland,  where  distilled  spirits 
are,  or  were,  freely  consumed,  gout  is  almost  un- 
known.      Moreover,   several   experiments    that    I 
have  made  indicate  that  alcohol,  in  such  quantities 
as  are  ever  likely  to  be  present  in  the  blood,  has 
no   efiect  either  upon   the   conversion  of  sodium 
quadriurate  into  biurate  or  on  the  solubility  of  the 
latter.      The   gout-inducing    properties    are   most 
probably  not  due  to  the  acids  of  the  wines  and 
beers,  for   the   reasons  which   have   already  been 
given.     They  are  also  most  probably  not  due  to  the 


148  Author's  Investigations. 

sugar.  The  late  Dr.  George  Harley  experimentally 
investigated  the  subject,  and  stated  that  the 
popular  notion  as  to  the  pernicious  effects  of  sugar 
in  cases  of  gout  is  open  to  grave  criticism,  seeing 
that  not  only  can  no  reliable  facts  be  adduced  in 
favour  of  the  statement,  but  no  reliable  authority 
for  the  assertion  can  be  cited  even  by  its  believers. 
1  have  myself  found  experimentally  that  sugar  has 
no  appreciable  effect  either  on  the  decomposition 
of  sodium  quadriurate,  or  on  the  solubility  of 
\  sodium  biurate. 

PROBABLE  CAUSE  OF  THE  GOUT- INDUCING  PROPERTIES 
OF  CERTAIN  WINES  AND  BEERS. 

The  gout-inducing  properties  are  certainly  not 
directly  due  to  the  oenanthic  ether  and  other 
ethereal  salts  of  wines  exerting  any  etlect  either  on 
the  rate  of  decomposition  of  the  sodium  quadriurate 
or  on  the  solubility  of  the  biurate.  To  demonstrate 
these  points  I  have  extracted  from  old  port  wines 
the  ethereal  salts  to  which  the  bouquet  of  the  wines 
is  due,  and  have  experimented  with  these  ethereal 
compounds  on  the  quadriurates  and  biurates. 
Using  quantities  far  in  excess  of  those  likely  to  be 
present  in  the  blood  after  the  moderate,  or  even 
immoderate,  consumption  of  such  wine,  I  find  that 
none  of  these  volatile  constituents  exercise  the 
slightest  effect  either  in  hastening  the  decomposi- 
tion of  the  sodium  quadriurate  or  in  diminishing 
the  solubiUty  or  hastening  the  precipitation  of 
sodium  biurate.  As  to  the  modus  ojyerandi  of 
certain  wines,  such  as  port,  etc.,  in  hastening  an 


PV/NBS  AND  Gout.  149 

attack  of  gout,  I  incline  to  the  opinion  that  the 
influence  of  wines  on  the  development  of  gout  is  in 
great  part  clue  to  the  eftect  they  exercise  on  the 
metabolism  of  the  liver,.. and. .  the- consequ^nt_i»— 
.  creased  amount  of  gljcocine  that  passes  on  to  the-' 
Jddneys.  This  increased  amount  of  glycocine 
would  then  cause  an  increased  production  of  uric 
acid  in  the  kidneys,  and  provided  there  be  deficient 
elimination  of  it  from  those  organs,  absorption  of 
the  surplus  uric  acid  wojili_laka„  place  into,  the 
ofeu£i'al  circulation.  At  the  same  time,  it  must  be 
remembered  that  those  accustomed  to  drink  wine 
are  also  able  to  indulge  in  other  luxuries  of  the 
table  which  greatly  favour  the  development  of 
gout 


i;o 


CHAPTER   XIL 

Experimental  investigation  of  the  relative  effects  exerted 
hy  the  mineral  constituents  of  various  vegetables 
on  the  solubility  of  sodium  biur ate— Experimental 
investigation  of  the  influence  exerted  by  the  mineral 
constituents  of  various  vegetables  in  retarding  the 
conversion  of  sodium  quadriurate  into  biurate — 
The  vegetables  most  beneficial  to  gouty  subjects. 

From  the  results  of  the  preUmuiar}^  experi- 
ments described  on  p.  144,  it  appears  probable 
that  if  the  mineral  constituents  of  vegetables  were 
present  in  sufficient  quantities  in  the  fluids  of  a 
gouty  person,  they  would  not  only  delay  the  advent 
of  an  attack  of  gout  by  increasing  the  solubility  of 
the  sodium  biurate  present  in  these  fluids,  but 
would  also,  by  their  increased  solvent  effects  on 
uratic  deposits,  facilitate  the  removal  of  the  latter. 
I  have  therefore  carried  out  a  long  series  of  ex- 
periments with  the  mineral  constituents  of  all  the 
vegetables  in  ordinary  use,  in  order  to  elucidate 
the  two  following  points :  (1)  the  relative  effects 
exerted  by  the  mineral  constituents  of  various 
vegetables  on  the  solubility  of  sodium  biurate  at 
the  temperature  of  the  human  body,  and  therefore 
presumably  on  uratic  deposits ;  and  (2)  the  in- 
fluence, if  any,  exerted  by  these  constituents  in 
retarding  the  conversion  of  the  sodium  quadri- 
urate, which  is  present  in  the  fluids  of  the  body 
in  gout,  into  the  sodium  biurate.     Obviously  the 


Experiments  with  Vegetable  Ashes.    151 


elucidation  of  these  points  would  have  a  material 
bearinor  on  the  treatment  of  f^out.* 

EXPERTMENTAL  mQUIRY  TO  ASCERTAIN  THE  SOLVENT 
EFFECTS  EXERTED  BY  THE  MINERAL  CONSTITUENTS 
OF  VARIOUS  VEGETABLES  ON  SODIUM  BI URATE. 

The  method  of  carrying  out  these  experiments 
was  similar  to  that  described  on  p.  142.  I  oper- 
ated separately  on  the  mineral  constituents  of  the 
following  vegetables: — Spinach,  Brussels  sprouts, 
potato,  asparagus,  Savoy  cabbage,  French  beans, 
lettuce,  beetroot,  winter  cabbage,  celery,  turnip 
tops,  turnip,  carrot,  cauliflower,  seakale,  and  green 
peas.  The  results  obtained  are  shown  in  the  fol- 
lowing sixteen  tables,  which  are  arranged  in  the 
order  of  the  average  solvent  effect  exerted  by  the 
mineral  constituents  of  the  various  vegetables,  com- 
mencing with  those  exercising  the  greatest  influence. 
The  solubility  of  sodium  biurate  in  distilled  water 
is  placed  at  the  head  of  each  table  for  comparison. 

TABLE    XVI. 

Showing  the  influence  of  the  mineral  constituents  of  spinach  on  the 
solubility  of  sodium  biurate  at  100°  F, 


Solvent 

Sodium  biurate 

dissolved. 

Water 

MO 

per  1.000 

Water  containing  : — 

rO  per  cent,  of  spinach  ash  ... 

3-36 

)> 

0-5            „                „           

2-76 

)> 

0-2            „                „           

2-12 

>> 

0-1             „                 „            

1-90 

j> 

0-05          „                „           

1-52 

)> 

0-02          „                „            

1-21 

»> 

o-oi          „               „           

lis 

>> 

*  The  results  of  these  experiments  were  first  communicated  to 
the  Koyal  Medical  and  Chirurgical  Society  of  London  in  a  paper 
read  on  June  14th,  1898. 


152 


A  UTHOR  '5  In  ves  tig  a  tions. 


TABLE   XVII. 

Allowing  the  influence  of  the  mineral  constituents  of  Brussels  sprouts 
on  the  solubility  of  sodium  biurate  at  100°  F. 


Solvent. 

Sodium  biurate 
dissolved. 

Water  ... 

110  per  1,000 

Water  containing  :— 

- 

1-0  per  cent,  of  Brussels  sprouts 

ash 

3-06 

,0-5                 „                   „ 

2-21         „ 

0-2                 „                   „ 

1-68         „ 

01 

1-62     .    „ 

005 

1-52         „ 

0-02 

1-30         „ 

0-01 

1-23 

TABLE   XVIII. 

Showing  the  influence  of  the  mineral  constituents  of  potato  on  the 
solubility  of  sodium  biurate  at  100°  F. 


Sodium  1 

biurate 

Solvent. 

dissol 

ved. 

Water  ... 

110  per 

1,000 

Water  containing  : — 

1-0  per  cent 

.of 

potato  ash    ... 

2-49 

05 

2-17 

0-2             „ 

1-92 

01             „ 

1-47 

005 

1-36 

0-02 

1-12 

0-01 

MO 

TABLE    XIX. 

Showing  the  influence  of  the  mineral  constituents  of  asparagus  on  the 
solubility  of  sodium  biurate  at  100°  F. 


Sodium  biurate 

Solvent. 

dissul 

ved. 

Water 

MO  per 

1,000 

Water  containing : — 

10  per  cent,  of  asparagus  ash 

2-77 

0-5                 „                 „                    

2-09 

0-2                 „                 „                    

1-58 

0-1             „             „                

1-45 

0-05               „                „                    

1-33 

002               „                 „                     

112 

0  01               „                 „                    

MO 

Experiments  with  Vegetable  Ashes.    153 

TABLE    XX. 

Shoiving  the  wflucnce  of  the  mineral  constitttents  of  Savoy  cabbage  on 
the  aolubilih/  of  sodium  hinyatc  at  100°  F. 


yodiuiii 

'iuratL- 

Sulvent. 

dissol 

ved. 

Water 

MO  pci 

1,000 

Water  containing  :  — 

1  '0  per  cent,  of  Savoy  cabbage  ash  ... 

2-32 

0-5                „                    „               

1-92 

0-2                „                    „                

1-77 

0-1            „               „           

1-57 

0-05               „                     „                

1-34 

0"2               „                     „                

1-13 

0-01               „                     „                

MO 

TABLE   XXI. 

Showing  the  influence  of  the  mineral  constituents  of  French  beans  on 
the  solubility  of  sodium  biurate  at  100°  F. 


Solvent. 


Sodium  l)inrate 
dissolved. 


Water 

Water  containing- : — 
10  per  cent,  of  French  beans  ash 
0-5 
0-2 
01 
005 
002 
001 


MO 

per 

1,000 

2-48 

1-87 

1-68 

1-56 

1-28 

1-16 

110 

TABLE    XXII. 

Showing  the  influence  of  the  mineral  constituents  of  lettuce  on  the 
solubility  of  sodium  biurate  at  100°  F. 


Sodium 

biurate 

Solvent. 

dissolved. 

Water 

MO  per  1,000 

Water  containing  : — 

rO  per  cent,  of  lettuce  ash  ... 

2-72 

0-5             ,,               ,,             

1-92 

0-2 

1-57 

0-1 

1-53 

0-05           „                „              

1-21 

0-02           „                „              

MO 

001           ,,               ,,             

1-09 

154 


A  UTHOR  's  Inves  tig  a  tions. 


TABLE    XXIII. 

Showinj  the  injlaenee  of  the  mineral  constituents  of  beetroot  on  the 
solabilitij  of  sodiicm  biurate  at  100°  F. 


Sodimii 

biurate 

Solvent. 

dissolved. 

Water 

Water  containing ;  — 

MOpe 

f  1,000 

1-0  per 

cent,  of  beetroot  ash  .. 

2-46 

>j 

0-5 

„                 ,, 

1-82 

?) 

0-2 

„                 „ 

1-60 

>> 

0-1 

,,                 ,, 

1-45 

>> 

0-05 

„                 ,,           ...         ... 

1-34 

5) 

0-02 

,,                 ,, 

1  15 

5» 

001 

,,                 „ 

MO 

)J 

TABLE    XXIV. 

Showing  the  injlaoice  of  the  mineral  constituents  of  winter  cabbage 
on  the  solubility  of  sodium  biurate  at  100°  F. 


Solvent. 

Sodium  biurate 
dissolved. 

Water  .. 

AVater  containing ; — 

MO  poi 

'  1,000 

rO  per  cent 

of  cabbage  ash 

2-30 

0-5 

., 

214 

0-2 

,, 

1-63 

01 

,, 

1-31 

0-05 

» 

1-23 

C-02 

i> 

MO 

0-01 

.,            ...         ...         ... 

MO 

TABLE    XXV. 

Shoicing  the  influence  of  the  mineral  constituents  of  celery  on  the 
solubility  of  sodium  biurate  at  100°  F. 


Solvent. 

Sodium 
disso] 

biurate 
ved. 

Water  ... 

11 0  per  1,000 

Water  containing :  — 

rO  per  cent. 

of 

celery  ash    ... 

2-20 

0-5 

1-84 

0-2 

1-53 

01 

1-44 

0-05           „ 

1-30 

002           „ 

1  10 

0-01           „ 

lOG 

Experiments  with  Vegetable  Ashes.    155 


TABLE    XXVI. 

Showing  the  influence  of  the  mineral  constituents  of  turnip  tops  on 
the  solubility  of  sodium  biurate  at  100°  F. 


Sodium 

)i  urate 

Solvent. 

dissol 

ved. 

Water 

1-10 

pel 

1,000 

Water  containing : — 

1  0  per 

ceni 

.  oft 

unip  tops  ash 

216 

0-5 

3> 

1-82 

0-2 

}J 

1-58 

0-1 

J» 

1-42 

O-Oo 

»J 

1-20 

0-02 

>  J 

l-Vi 

0-01 

1-11 

TABLE    XXVIL 

Showing  the  influence  of  the  mineral  constituents  of  turnips  on  the 
solubility  of  sodium  biurate  at  100^  F. 


Sodium  biurate 

Solvent. 

di 

ssolved. 

Water 

MO 

per  1,000 

Water  containing  : — 

1-0  per  cent,  of  turnip  ash   ... 

2-Oi 

0-5              „                  „            

1-78 

0-2             „                 „            

1-50 

0-1         „            „        

1-42 

0-05           „                 „            

1-32 

0-02           „                 „            

1-U 

0-01           „                 „            

MO 

TABLE    XXYin. 

Shoiving  the  influence  of  the  mineral  constituents  of  carrot  on  the 


solubility  of  sodium  biurate  at  100° 

F. 

Solvent. 

Sodium  biurate 
dissolved. 

Water 

Water  containing : — 

1-10  per 

1,000 

10  per 

cent,  of  carrot  ash    ... 

1-63 

05 

1-53 

0-2 

1-47 

0-1 

1-4.5 

0-05 

1-33 

0  02 

1-13 

0-01 

Ml 

•> 

156 


A  UTHOR  's  In  ves  tig  a  tions. 


TABLE    XXIX. 

Show'inj  the  hiflncncc  of  the  mineral  comtituenta  of  cauVijlower  on  the 
solubility  of  sodium  biurate  at  100"  F. 


Solvent. 


Water 

Water  containing  : 
I'O  per  cent,  of  cauliflower  ash. 

o-i 

0-05 
002 
001 


So'linm 
clissol 

ilurate 
i-ed. 

MO 

pel 

1,000 

l-o2 
1-50 

5» 

1-42 

5» 

1-3-t 

5? 

1-28 
1-09 

5» 

1-09 

TABLE    XXX. 

Showing  the  injfuence  of  the  mineral  constituents  of  seakale  on  the 
solubility  of  sodium  biurate  at  100"  F. 


Solvent. 


Water 

Water  containing 
1  0  per  cent,  of  seakale  ash 
0-5  ,,  „ 

0-2 
01 
O-Oo 
0-02 
001 


Sodium 

li  urate 

dissol 

ved. 

110  per 

1,000 

1-49 

>> 

1-47 

>» 

1-3.5 

5» 

1-23 

■» 

110 

9» 

110 

>» 

MO 

TABLE   XXXI. 

Shotcing  the  influence  of  the  mineral  constituents  of  green  peas  on  the 
solubility  of  sodium  biurate  at  100"  F. 


Solvent. 


Water...         

Water  containing : 
10  per  cent,  of  gieen  peas  ash 
Co  „  „ 

0-2 
0-1 
005 
002 
o-oi 


Sodium 

biurate 

dis.so 

Ived. 

MO  per  1,000 

0-99 

101 

104 

110 

110 

110 

MO 

Experiments  with  Vegetable  Ashes.    157 

From  the  results  detailed  in  these  tables  it  is 
evident  that  0"05  per  cent,  and  over  of  the  mineral 
constituents  of  nearly  all  the  vegetables  very 
appreciably  increases  the  solubility  of  sodium  bi- 
urate.  The  sohtary  exception  is  in  the  case  of  the 
mineral  constituents  of  green  peas,  which  practically 
exert  no  influence  whatever  on  the  solubility  of 
the  biurate. 

As  I  considered  that  these  solvent  effects  of 
the  mineral  constituents  of  most  vegetables  on  the 
biurate  might  have  an  important  bearing  on  the 
treatment  of  gout,  I  next  endeavoured  to  ascertain 
whether  these  effects  were  due  to  the  alkalinity  of 
the  vegetable  ashes,  or  whether  they  could  be 
referred  to  any  one  saline  constituent  of  the 
vegetables. 

EXPERIMENTAL  PROOF  THAT  THE  SOLVENT  EFFECTS 
OF  THE  MINERAL  CONSTITUENTS  OF  VEGETABLES 
ON  SODIUM  BIURATE  ARE  NOT  DUE  TO  THEIR 
DEGREE  OF  ALKALINITY. 

That  the  solvent  effect  exerted  respectively  by 
the  mineral  constituents  of  each  vesretable  on  the 
sodium  biurate  was  not  proportional  to  the  alka- 
linity of  the  ash  was  very  easily  determmed.  I 
made  estimations  of  the  alkalinities  of  the  different 
vegetable  ashes,  and  calculated  the  percentages  of 
alkalinity  in  terms  of  sodium  carbonate.  The 
alkalinity  of  the  ashes  was  due  to  potassium  and 
sodium  carbonates ;  none  of  the  ashes  contained 
either  potassium  or  sodium  hydrate.  The  follow- 
ing table   shows   a   comparison   of  the   solubilit}' 


158 


A  UTHOR  's  In  ves  tig  a  tions. 


exerted  by  the  mineral  constituents  of  vegetables 
on  sodium  biurate,  and  the  alkalinity  of  thos3  con- 
stituents. 

TABLE    XXXir. 

Shoiving  that  the  solvent  effect  on  sodium  biurate  of  the  mineral 
constituents  of  vegetables  is  not  dependent  on  the  alkalinity  of 
those  constituents. 


Vegetables  arranged  in  order 

of  solvent  effect  of  tlieir 

Vegetables  arranged  in 

order  of  the  alkalinity 

mineral    constituents    on 

of  their  ashes,  and 

showing 

percentages  of 

sodium     biurate.      Com- 

alkalinity reckoned 

as  sodium    carbonate. 

mencing  with  tliose  exert-  | 

Commencing  with  the  most  alkaline. 

ing  the  greatest  effect. 

Spinach 

Spinach  ... 

26-00 

Brussels  sprouts 

Celery     ... 

20-80 

Potato 

Turnip    ... 

20-80 

Asparagus 

Potato     

17-55 

Savoy  cabbage 

Beetroot ... 

15-60 

French  beans 

Cauliflower 

13-20 

Lettuce 

Carrot     ... 

1300 

Beetroot 

Brussels  sprouts 

12-35 

Cabbage                      ' 

French  beans    ... 

12-35 

Celery 

Turnip  tops 

11-70 

Turnip  tops 

Lettuce  ... 

11-05 

Turnip 

Asparagus 

8-45 

Carrot 

Cabbage 

5-85 

Cauliflower 

Green  peas 

5-20 

Seakale 

Savoy  cabbage  ... 

4-55 

Green  peas 

Seakale 

1-95 

It  is  evident  from  a  glance  at  this  table  that 
the  solvent  effect  of  a  vegetable  ash  on  sodium 
biurate,  with  the  exception  of  spinach  ash,  bears  no 
relationship,  either  of  a  direct  or  an  inverse  ratio, 
to  the  alkalinity  of  the  ash.  For  instance,  it  can 
be  seen  that  the  solvent  effect  on  the  biurate  of  the 
ash  of  Brussels  sprouts  is  high,  Avhile  its  alkalinity 
is  low ;  on  the  other  hand,  the  solvent  efi'ect  on  the 
biurate  of  the  ash  of  celery  is  low,  while  its  alka- 
linity is  high.  In  other  words,  it  is  evident  that 
the  order  in  which  the  vegetables  are  arranged  as 


Experiments  with  Vegetable  Ashes.   159 

reofards  the  solvent  effect  of  the  mineral  con- 
stituents  on  the  biurate  is  neither  the  order  nor 
the  inverse  order  of  their  relative  alkalinities. 
These  results  support  the  conclusions  I  arrived  at 
from  some  experiments  made  with  blood  serum, 
and  described  in  the  "  Goulstonian  Lectures ''  of 
1897.  I  then  showed  that  a  diminution  in  the 
alkalinity  of  blood  serum  did  not  cause  a  diminu- 
tion in  the  solvent  power  of  the  serum  for  biurate, 
and,  conversely,  that  an  increase  in  the  alkalinity 
of  the  serum  did  not  increase  its  solvent  power  for 
the  biurate. 

EXPERIMENTAL  PROOF  THAT  THE  SOLVENT  EFFECTS 
OF  THE  MINERAL  CONSTITUENTS  OF  VEGETABLES 
ON  SODIUM  BIURATE  ARE  NOT  DUE  TO  ANY 
SINGLE   CONSTITUENT. 

The  next  problem  to  solve  was  whether  the 
effect  exerted  by  the  mineral  constituents  of 
vegetables  in  increasing  the  solubility  of  sodium 
biurate  is  due  to  any  one  constituent.  With  regard 
to  this  point,  it  appeared  probable  before  hand  that 
such  would  not  prove  to  be  the  case,  since  Sir 
William  Roberts  has  shown  that  sodium,  calcium, 
and  magnesium  salts  diminish  the  solvent  power 
of  water  on  sodium  biurate,  and  that  ]3otassium 
salts  exercise  no  influence,  one  way  or  the  other,  on 
the  solubility  of  the  biurate. 

Now  it  can  easily  be  demonstrated  that  the 
solvent  effect  is  not  due  to  the  potassium  salts.  The 
following  table  contains  a  comparison  of  the  solvent 
powers   exerted    by    the    mineral   constituents   of 


i6o 


A  UTHOR  's  In  ves  tig  a  tions. 


vegetables  on  sodium  biurate,  and  the  proportions 
of  potassium  salts  present. 

TABLE    XXXIII. 

Showing  that  the  solvent  ejf'ect  on  sodium  biurate  of  the  mineral 
constituents  of  vegetables  is  not  dependent  on  the  amounts  of 
potassium  salts  present. 


Vegetables  arranged  in  order 

Vegetables  arranged  in  order  of  the  ; 

iroportions 

of  solvent  effect  of  their 

of  potassium  salts  present,  and  showing  the 

mineral    constituents    on 

percentages  of  potassium   salts 

present  in 

sodium     biurate.      Com- 

the   ashes,   reckoned  as    potassium    oxide. 

mencing  with  tliose  exert- 

Commencing with  those  richest  in 

pota.ssiuni 

ing  the  greatest  etfect. 

salts. 

Spinach 

Potato      

..      56-03 

Brussels  sprouts 

Turnip    ... 

..     5405 

Potato 

Carrot     ... 

..     53-36 

Asparagus 

Lettuce  ... 

..     48-01 

Savoy  cabbage 

J^renehbeans     

..     46-50 

Freuch  beans 

Asparagus 

..     39-21 

Lettuce 

Green  peas 

..     38-96 

Beetroot 

Beetroot 

..     38-33 

Cabbage 

Cabbage ... 

..     37-71 

Celery 

Brussels  sprouts 

..     35-00 

Turnip  tops 

Celery     ... 

..     3314 

Tui-nip 

Turnip  tops 

..     30-55 

Carrot 

Savoy  cabbage  ... 

..     26-82 

Cauliflower 

Cauliflower 

..     23-46 

Seakale 

Spinach  ... 

..     23-43 

Green  peas 

Seakale  ... 

2-59 

It  is  also  evident  from  this  table  that  the  solvent 
effect  of  the  mineral  constituents  of  ves^etables  on 
sodium  biurate  bears  no  relationship,  either  of  a 
direct  or  an  inverse  ratio,  to  the  proportions  of 
potassium  salts  present.  For  instance,  it  can  be 
seen  that  the  solvent  effect  on  the  biurate  of  the 
ash  of  spinach  is  high,  while  the  proportion  of 
potassium  salts  is  low ;  on  the  other  hand,  the  solv- 
ent effect  on  the  biurate  of  the  ash  of  turnips  is  low, 
while  the  proportion  of  potassium  salts  is  high. 

It  can  also  be  demonstrated  that  the  increased 


Sodium  Salts  ix   Vf.getadles. 


i6i 


solubility  of  the  biurate  effected  by  the  inineral 
constituents  of  vegetables  is  not  due  to  the  sodium 
salts.  The  following  table  contains  a  comparison 
of  the  solvent  powers  exerted  by  the  inineral  con- 
stituents of  vegetables  on  sorlium  biurate,  and  the 
proportions  of  sodium  salts  present. 

TABLE  XXXIV. 

Showlnj  that  the  solvent  effact  on  sodium  binrate  of  the  minercl 
constituents  of  vegetables  is  not  dependent  oil  the  amoioits  <f 
sodium  salts  present. 


VfL^otubles  arranged  in  or-lcr 
uF  solvent  etl'ect  of  their 
iiiiiieral  constituents  on 
sodium  biurate.  Com- 
mencing witli  those  exert- 
ing the  greatest  effect. 


Vegetables  arranged  in  onlerof  the  proportions 
of  sodium  salts  i>resent  and  showing  the 
percent  iges  of  sudium  salts  present  in  the 
ashes,  reckoned  as  sodium  oxide.  Com- 
mencing with  those  richest  in  sodium  salts. 


Spinuch 

Serikale  ... 

...     33-84 

Brussels  sprouts 

Spinach  ... 

...      31-42 

Potato 

Beetioot... 

...     31-17 

Asparagus 

French  beans     ... 

...     30-50 

.S.tvoy  cabbage 

Celery     ... 

...     19-33 

French  beaus 

Asparagus 

...      16-79 

Lettuce 

Carrot 

..       1417 

Beetioot 

Savoy  cabbage  .  , 

...      13-86 

Cabbctge 

Brussels  sprouts 

...      12-60 

Celei  y 

Lettuce 

...      11-80 

Turnip  tops 

Cauliflower 

...     in-87 

Turnip 

Turnip    ... 

...       6-37 

Carrot 

Gieen  peas 

5-20 

Cauliflower 

Turnip  toi)S 

4-19 

ISeakale 

Cabbage ... 

2-:;9 

Green  peas 

i'otato     ... 

21S 

It  is  evident  from  this  table  that  the  solvent 
effect  of  the  mineral  constituents  of  vegetables  on 
sodium  biurate  bears  no  relationsbip,  either  of  a 
direct  or  an  inverse  ratio,  to  the  proportions  of 
sodium  salts  present.  For  instance,  it  can  be  seen 
that  the  solvent  effect  on  the  biurate  of  the  ash  of 
potato  is  high,  while  the  proportion  of  sodium  salts 
is  low :  on  the  other  hand,  the  solvent  effect  on  the 


1 62 


A  UTHOR  's  Inves  tig  a  tions. 


biurate  of  the  ash  of  seakale  is  low,  while  the  pro- 
portion of  sodium  salts  is  high. 

In  like  manner  it  can  be  demonstrated  that  the 
increased  solubility  of  the  biurate  effected  by  the 
mineral  constituents  of  vegetables  is  not  due  to  the 
calcium  salts.  The  following  table  contains  a 
comparison  of  the  solvent  powers  exerted  by  the 
mineral  constituents  of  vegetables  on  sodium  bi- 
urate, and  the  proportions  of  calcium  salts  present. 

TABLE  XXXV. 

Showing    that    the  solvent  effect   on   sodium  biurate   of  the  mineral 
constituents   of  vegetables  is   not  dependent  on  the  amoimts  of 

calciuin  sal's  present. 


Vegetables  arranged  in  order 
of  solvent  etfect  of  tlieir 
mineral  constituents  on 
sodium  biurate.  Com- 
mencing witli  those  exert- 
ing the  greatest  effect. 


Vegetables  arranged  in  orderof  the  proportions 
of  calcium  salts  present,  and  showing  the 
percentages  of  calcium  salts  present  in  the 
ashes,  reckoned  as  calcium  oxiile.  Com- 
mencing with  those  richest  in  calcium  salts. 


Spinach 

Turnip  tops       

...     37-15 

Brussels  sprouts 

Seakale  ... 

...     27 -56 

Totato 

Cauliflower 

...     23  33 

Asparagus 

French  beans     ... 

...     17-48 

Savoy  cabbag-e 

Cabbage 

...     17-14 

French  beans 

Lettuce  ... 

...      15-02 

Lettuce 

Savoy  cabbage  ... 

...     14-83 

Beetroot 

Turnip    ... 

...     13-38 

Cabbage 

Celery     ... 

...     13-03 

Celery 

Spinach ...         

...     10-64 

Turnip  tops 

Carrot     ...         

...       6-88 

Turnip 

Brussels  sprouts 

...       616 

Carrot 

Potato 

...       5-46 

Cauliflower 

Asparagus 

...       505 

Seakale 

Green  peas 

...       4-98 

Green  peas 

Beetroot...         

...       2-58 

It  is  also  evident  from  this  table  that  the 
solvent  effect  of  the  mineral  constituents  of  vege- 
tables on  sodium  biurate  bears  no  relationship, 
either  of  a  direct  or  an  inverse  ratio,  to  the  propor- 
tions of  calcium  salts  present.     For  instance,  it  can 


Phosphates  in  Vegetables, 


163 


be  seen  that  the  solvent  effect  on  the  biurate  of 
the  ash  of  potato  is  high,  while  the  proportion  of 
calcium  salts  is  low ;  on  the  other  hand,  the  solvent 
effect  on  the  biurate  of  the  ash  of  seakale  is  low, 
while  the  proportion  of  calcium  salts  is  high. 

Similarly  it  can  be  shown  that  the  increased 
solvent  effect  on  the  biurate  exerted  by  the  mineral 
constituents  of  vegetables  is  not  due  to  either  the 
magnesium  or  iron  salts  present. 

It  can  also  be  demonstrated  that  the  increased 
solubility  of  the  biurate  is  not  due  to  the  phos- 
phates present  in  the  vegetables.  The  following 
table  contains  a  comparison  of  the  solvent  powers 
exerted  by  the  mineral  constituents  of  vegetables 
on  sodium  biurate,  and  the  proportions  of  phos- 
phates present. 

TABLE    XXXYI. 

Showing  that  the  solvent  efftct  on  sodium  biurate  of  the  mineral 
constituents  of  vegetables  is  not  dependent  on  the  amounts  of 
phosphates  present. 


Vegetables  arranged  in  order 
of  solvent  effect  of  their 
mineral  constituents  on 
sodium  biurate.  Com- 
mencing witli  those  exert- 
ing the  greatest  eftect. 


Spinach 

Brussels  sprouts 

Potato 

Asparagus 

Savoy  cabbage 

French  beans 

Lettuce 

Beetroot 

Cabbage 

Celery 

Turnip  tops 

Turnip 

Carrot 

Cauliflower 

Seakale 

Green  peas 


Vegetables  arranged  in  order  of  the  proportions 
of  phosphates  present,  and  showing  the 
percentages  of  phosphates  present  in  the 
ashes,  reckoned  as  phosphoric  anhydride. 
Commencing  witli  those  ricliest  in'  phos- 
phates. 


Green  peas 

35-62 

Cauliflower 

22-14 

Asparagus 

21-93 

Potato     

15-99 

CaiTot     ... 

15-02 

Celery     ... 

14-39 

Brussels  sprouts 

14-20 

Savoy  cabbage  ... 

13-19 

French  beans     . . . 

12-21 

Cabbage... 

11-99 

Ijettuce  ... 

9-62 

Turnip    ... 

9-26 

Spinach  ... 

8-56 

Beetroot... 

...       8-25 

Seakale  ... 

800 

Turnip  tops 

6-15 

164 


Author  's  Ix  i  'es  tig  a  t/ons. 


It  is  also  evident  from  this  tabie  that  the  solv- 
ent effect  of  the  mineral  constituents  of  vegetables 
on  sodium  biurate  bears  no  relationship,  either  of 
a  direct  or  an  inverse  ratio,  to  the  proportions  of 
phosphates  present.  For  instance,  it  can  be  seen 
that  the  solvent  effect  on  the  biurate  of  the  ash  of 
spinach  is  high,  Avhile  the  proportion  of  phosphates 
is  low  :  on  the  other  hand,  the  solvent  effect  on  the 
biurate  of  the  ash  of  green  peas  is  low,  Avhile  the 
proportion  of  phosphates  is  high. 

It  can  also  be  demonstrated  that  the  increased 
solubility  of  the  biurate  is  not  due  to  the  sulphates 
present  in  the  vegetables.  The  following  table  con- 
tains a  comparison  of  the  solvent  powers  exerted  by 
the  mineral  constituents  of  vegetables  on  sodium 
biurate,  and  the  proportions  of  sulphates  present. 

TABLE    XXXVII. 
>ihowinfj  that  the  solvent  effect  on  so  ii  -m  hlurateofthe  m'lneraJ  constitueydfs 

of  vegetables  is  not  dependent  ou  the  amounts  of  sulphates  present. 


Vegetables  arranged  in  onler  j 
of  solvent  effect  of  their  j 
mineral    constituents    on  ; 
sodium     biurate.       Com 
mencing  with  those  exert 
ing  the  greatest  effect. 


Vegetables  arranged  in  order  of  the  proportions 
of  sulphates  present,  and  showing  the  per- 
centages of  sulphates  pi-csent  in  the  ashes, 
reckoned  as  sulphuric  anhydride.  Com- 
mencing  with  those  richest  in  suljihates. 


Si)inach 

Brussels  sprouts 

Potato 

Asparagus 

Savoy  cabbage 

French  beans 

Lettuce 

Beetroot 

Cabbage 

Celery 

Turnip  tops 

Turni]) 

Carrot 

Cauliflower 

Seakale 

Green  peas 


Seakale  ... 

...      19-78 

Turnip  U)\)< 

...     15-27 

Cauliflower 

...      141(3 

Savoy  cabbitge  ... 

...      12-8.) 

Turnip    ... 
Brussels  sprouts 
Cabbage 
French  beans    ... 

...  12-47 
...  8-31 
...  7-28 
...       6-82 

Potato 

...       5-60 

Asparagus 
Carrot     ... 

5-40 
...       5-20 

Spinach  ... 

...       4-44 

Green  peas 

4-36 

Lettuce  ... 

3-92 

Beetroot... 

...        2-4  1 

Celerv 

1-10 

Chlorides  in  Vp.gktadlbs. 


165 


It  is  also  evident  from  this  table  that  the  solv- 
ent effect  of  the  mineral  constituents  of  vegetables 
on  sodium  biurate  bears  no  relationship,  either  of  a 
direct  or  an  inverse  ratio,  to  the  proportions  of 
sulphates  present.  For  instance,  it  can  be  seen 
that  the  solvent  etfect  on  the  biurate  of  the  ash  of 
spinach  is  high,  while  the  proportion  of  sulphates 
is  low ;  on  the  other  hand,  the  solvent  effect  on  the 
biurate  of  the  ash  of  seakale  is  low,  while  the 
proportion  of  sulphates  is  high. 

Finally,  as  disposing  of  all  the  mineral  con- 
stituents of  any  importance  in  vegetables,  it  can  bo 
demonstrated  that  the  increased  solubility  of  the 
biurate  is  not  due  to  the  chlorides  present  in  the 
vegetables,  as  seen  in  the  following  table. 

TABLE    XXXVIII. 

Shoiving  that  the  solvent  (ffcct  on  scdium  biurate  of  the  mineral 
constituents  of  vegetables  is  not  dependent  on  the  amounts  of 
chlorides  present. 


Vegetables  arranged  in  order 

of  solvent  ettect  of  their 

Vegetables  arranged  in  order  of  tlie  proportion 

mineral    constituents    on 

of  chlorides  present, 

and  showing  tlie  per- 

sodinni     biurate.       Com- 

centages of  chlorides 

present  in  the  ashes, 

mencing  with  those  exert- 
ing the  greatest  effect. 

reckoued  as   chlorine.      Commencing    with 
those  richest  in  chlorides. 

Spinach 

Celery     ... 

2214 

]3russels  sprouts 

Beetroot... 

18-13 

Potato 

Seakale  ... 

15-46 

Asparagus 

Cabbage ... 

9-09 

Savoy  cabbag-e 

Lettuce  ... 

8-80 

French  beans 

Spinach  ... 

7-78 

Lettuce 

Savoy  cabbage  . . . 

7-53 

Jicetroot 

Turnip  tops 

7-33 

Cabbage 

Asparagus 

6-62 

Celery 

Turnij)    ... 

6-06 

Turnip  toi)S 

Cauliflower 

4-83 

Turnip 

Carrot     ... 

3-70 

Carrot 

Brussels  sprouts 

3-00 

Cauliflower 

Potato     

2-50 

Seakale 

French  beans     . . . 

2-50 

Green  peas 

Green  peas 

2-10 

1 66  Author's  Investigations. 

It  is  also  evident  from  this  table  that  the  solv- 
ent effect  of  the  mineral  constituents  of  vegetables 
on  sodium  biurate  bears  no  relationship,  either  of  a 
direct  or  an  inverse  ratio,  to  the  projDortions  of 
chlorides  present.  For  instance,  it  can  be  seen 
that  the  solvent  effect  on  the  biurate  of  the  ash  of 
Brussels  sprouts  is  high,  while  the  proportion  of 
chlorides  is  low ;  on  the  other  hand,  the  solvent 
effect  on  the  biurate  of  the  ash  of  seakale  is  low, 
while  the  proportion  of  chlorides  is  high. 

These  results  collectively  show  that  the  solvent 
effect  exerted  on  sodium  biurate  by  the  mineral 
constituents  of  vegetables  is  not  due  to  any  one 
constituent. 

EXPERIMENTAL  PROOF  THAT  AN  ARTIFICIALLY  PRE- 
PARED ASH  DOES  NOT  REACT  TO  SODIUM  BIURATE 
IN  THE  SAME  MANNER  AS  A  NATURAL  VEGETABLE 
ASH. 

I  next  endeavoured  to  ascertain  whether  an 
artificially  prepared  ash  of  the  same  composition  as 
the  natural  ash  of  one  of  the  vegetables  would 
exercise  a  similar  effect  in  increasing  the  solubility 
of  the  sodium  biurate  to  that  possessed  by  the 
natural  ash.  For  this  purpose  I  selected  the 
spinach  ash,  which  has  the  greatest  solvent  effect  on 
the  biurate.  An  artificial  ash  was  prepared,  which 
was  made  with  the  same  proportions  of  potassium, 
sodium,  calcium,  sulphates,  phosphates  and  chlor- 
ides as  those  present  in  the  natural  spinach  ash, 
and  also  of  precisely  the  same  degree  of  alkalinity. 
Experiments  were  carried  out  with   this  artificial 


Artificial  and  Natural  Ash. 


167 


ash  and  the  biurate  in  a  similar  manner  to  that 
employed  in  working  with  the  natural  vegetable 
ashes.  The  following  table  shows  the  results  of 
these  experiments: — 

TABLE    XXXIX. 

Showing  the  influence  of  the  artificial  spinach  ash  on  the  solubility  of 


sodium  biurate  at  100°  F. 

Solvent. 

Sodium 
dissol 

biurate 
ved. 

Water 

1-10  per 

1,000 

Water  containing  : — 

1-0  per  cent,  of  artificial  spinach  ash. 

0-20 

0-5 

0-34 

0-2 

0-62 

0-1 

0-86 

0-05 

0-96 

0-02 

1-04 

0-01 

1-06 

These  results  are  very  remarkable,  as  they  in- 
dicate that  the  artificial  ash  exercises  in  all  pro- 
portions a  deterrent  effect  on  the  solubility  of  the 
biurate.  This  deterrent  effect  is  well  seen  by  con- 
trasting the  results  with  those  of  the  natural  ash, 
which  show  the  marked  solvent  effect  exerted  by 
the  latter  on  the  biurate. 

TABLE    XL. 

Shoicing  the  different  influences  exerted  by  the  artificial  and  natural 
spinach  ashes  on  the  solve)ic>j  of  the  biurate  at  100°  F. 


Solvent. 

Sodi 

uni  biurate  dissolved  iu  1,000  parts. 

Water         

MO 

Artificial  spinach  asli. 

Natural  spinach  ash. 

Water  containing : — 

I'D  per  cent,  of  ash 

0  20 

3-36 

O-o 

0-34 

276 

0-2 

0-62 

2-12 

0-1 

0-86 

1-90 

0  05        „ 

0-96 

1-52 

0-02         „ 

1-04 

1-21 

001        „ 

1-06 

1-18 

1 68 


A  UTHOR  5    L\  I  '£S  TIG  A  TIONS. 


The  only  explanation  that  I  can  oifer  of  these 

remarkable  results  is  that  in  the  natural  ash  there 

is  some  combination   of  the  mineral  constituents 

Avhieh  cannot  be  artificial!}^  imitated,  and  that  upon 

this  natural  combination  of  the  salts  is  dependent 

the  increased  solvent  effect  exerted  on  the  biurate 

by  the  mineral  constituents  of  most  vegetables.     If 

this  view  be  correct,  then  modern  science  is  but 
> 

confirming  the  correctness  of  the  practice  of  those 
ancients  who  employed  vegetable  ashes  in  the 
treatment  of  gout. 

It  is  well  to  make  here  a  brief  reference  to  the 
experiments  described  on  p.  143,  which  show  that 
the  mineral  constituents  of  meat  exercise  a  marked 
deterrent  effect  on  the  solubility  of  sodium  biurate  ; 
and  that  this  effect  is  most  marked  by  proportions 
of  the  mineral  constituents  which  may  certainly  be 
present  in  the  blood  after  eating  a  few  ounces  of 
meat.  The  following  table  shows  in  contrast  the 
effects  exercised  respectively  by  the  mineral  con- 
stituents of  lean  beef  and  spinach  on  the  solubility 
of  the  biurate. 

TABLE    XLI. 

Showing  the  respective  effects  exercised  by  the  minernl  constituents  of 
beef  and  spinach  on  the  solnbdity  of  sodium  biurate  at  100°  F. 


Solvent. 


odium  biurate  dissolved  in  1,000  parts. 


Water 

r  cont^iininc^  :  — 

1] 

10 

Beef  ash. 

Spinach  asli. 

Wat€ 

10  per 

cent. 

of  ash 

0-93 

3-36 

0  o 

0-76 

2-76 

0  2 

»>                           ... 

0-56 

2-12 

0  1 

0  32 

1-90 

0(.5 

0  1 5 

1  -02 

0  02 

0-11 

1-21 

001 

,. 

0-85 

118 

Vegetable  Ashes  and  Quadriurate.     169 

expellimental  inquiry  to  ascertain  the  effect 
exerted  by  the  mineral  constituents  of 
various  veoetables  on  the  conversion  of 
sodium  quadriurate  into  sodium  biurate. 

It  is  well  known  from  the  researches  of 
Dr.  Bence  Jones  and  of  Sir  William  Roberts  that 
sodium  quadriurate,  which  is  the  form  in  Avhich 
uric  acid  first  appears  in  the  blood  in  gout,  is  an 
unstable  body,  and  is  gradually  converted  by  com- 
bination with  the  sodium  carbonate  of  the  blood 
into  sodium  biurate,  which  latter  body,  on  account 
of  its  comparative  insolubility,  deposits  in  the 
tissues  and  thus  constitutes  the  gouty  uratic 
deposit.  This  gradual  conversion  of  the  quadri- 
urate into  biurate  is  known  as  the  matviration 
iwocess. 

It  is  obviously  of  therapeutical  importance  to 
know  whether  the  mineral  constituents  of  any  of 
the  vegetables,  in  addition  to  exerting  an  increased 
solvent  effect  on  the  biurate,  possess  the  power 
of  delaying  this  maturation  process;  or,  in  other 
words,  of  inhibiting  the  conversion  of  the  quadri- 
urate into  the  biurate.  In  order  to  ascertain  this, 
I  conducted  a  series  of  experiments.  In  all  these 
experiments  I  employed  Sir  William  Roberts's 
standard  solution,  as  being  a  more  convenient 
medium  to  work  with  than  blood  serum.  This 
standard  solution  contains  Ob  per  cent,  of  sodium 
chloride  and  0*2  per  cent,  of  sodium  bicarbon- 
ate dissolved  in  distilled  water.  Sir  William 
Roberts  found  that  this  solution  is  a  fairly  exact 


170  Author's  Investigations. 

representation  of  blood  serum,  in  so  far  as  its  saline 
ingredients  are  concerned,  and  that  it  reacted 
with  uric  acid  and  the  urates  in  the  same  manner 
as  blood  serum  itself,  and  in  the  same  manner  as 
a  solution  comprising  all  the  salines  of  the  serum 
in  their  due  proportions. 

The  experiments  were  conducted  in  the  follow- 
ing way. 

Pure  sodium  quadriurate  was  prepared  by 
shaking  for  one  minute  ten  grammes  of  uric  acid 
with  a  litre  of  a  boiling  hot  5  per  cent,  solution 
of  sodium  acetate.  This  was  filtered  hot,  and  the 
filtrate  was  then  rapidly  cooled  on  ice.  The  quad- 
riurate, which  falls  down,  was  at  once  collected  on 
a  filter,  washed  with  absolute  alcohol,  and  dried 
at  100°  F.  Ten  milligrammes  of  pure  sodium 
quadriurate  were  well  rubbed  with  ten  drops  of 
the  standard  solution,  and  the  mixture  placed  in 
a  small  corked  bottle  in  the  warm  chamber  and 
kept  at  100°  F.  Every  half-hour  a  small  quantity 
of  the  mixture  was  examined  under  a  high  power 
of  the  microscope,  and  the  time  at  which  crystals 
of  sodium  biurate  first  appeared  was  noted.  This 
represented  the  time  occupied  by  the  maturation 
process  when  the  standard  solution  was  saturated 
with  sodium  quadriurate.  Similar  experiments 
were  conducted  with  the  same  amount  of  sodium 
quadriurate  in  the  same  quantity  of  standard  solu- 
tion containing  respectively  01  per  cent,  of  the 
mineral  constituents  of  each  of  the  vegetables  in 
ordinary  use.  The  results  are  shown  in  the  follow- 
ing table. 


Vegetable  Ashes  and  Quadriurate.     171 


TABLE    XLII. 

Showing  the  effects  exerted  by  the  mineral  constituents  of  vegetables  on 
the  conversion  of  sodium  qtiadrinrate  into  sodium  biurate. 


Cry.stals  of  sodium  biuiate 

Solvent. 

first  appeared  in  — 

Standard  sol 

ntion 

2  hours 

Standard  solution  containing  :  — 

0-1  per  cent. 

of  potato  ash 

2 

cauliflower  ash... 

2 

lettuce          „   ... 

2 

carrot             ,,   ... 

2 

asparagus     ,,  ... 

2i 

beetroot        ,,   ... 

3 

green  peas    „   ... 

3| 

celery           ,,   ... 

3^ 

Brussels  sprouts  ash   . . . 

4 

cabbage                , , 

4 

' 

turnip  tops           ,, 

4 

turnip                    ,, 

4 

SaA^oy  cabbage     , . 

4 

seakale                  ,, 

4 

French  beans        ,, 

H 

spinach                  „ 

5 

These  results  show  that  the  mineral  constituents 
of  some  of  the  vegetables — notably  spinach,  Brussels 
sprouts,  French  beans,  cabbage,  turnip  tops,  and 
turnips — very  considerably  delay  the  conversion  of 
sodium  quadriurate  into  sodium  biurate.  The  in- 
ference is  that  if  such  mineral  constituents  were 
present  in  suitable  proportions  in  the  blood  of 
gouty  subjects,  and  if,  at  the  same  time,  proper 
measures  were  adopted  for  promoting  excretion  of 
the  quadriurate  by  the  kidneys,  the  elimination  of 
that  body  might  be  secured  without  the  occurrence 
of  any  precipitation  of  the  biurate  in  the  tissues. 
Moreover,  it  must  be  borne  in  mind  that  these 
experiments  were  conducted  under  very  stringent 
conditions,  in  that  they  were  all  carried  out  with  a 


172  A  UTHOR  's  In  ves  tig  a  tions. 

saturated  solution  of  tlie  quadriurate,  and  it  is 
extremely  unlikely  that  the  fluids  of  the  body  are 
ever,  in  gouty  subjects,  saturated  with  so  soluble  a 
compound  as  the  sodium  quadriurate ;  therefore,  it 
is  but  fair  to  infer  that,  with  smaller  proportions  of 
the  quadriurate  in  solution,  the  inhibitory  efifects  of 
the  mineral  constituents  of  vegetables  woidd  extend 
over  much  longer  periods  than  actually  occurred 
in  the  carrying  out  of  these  experiments. 

RESULTS    OF   THE    EXPERIMENTAL    INQUIRY. 

The  net  residts  of  all  the  experiments  de- 
scribed indicate  that  the  mineral  constituents  of 
most  vegetables  increase  the  solubility  of  sodium 
biurate,  and  also,  in  several  cases,  delay  for  con- 
siderable periods  the  conversion  of  the  sodium 
quadriurate  into  the  biurate.  On  the  other  hand, 
the  mineral  constituents  of  meat  diminish  the 
solubility  of  sodium  biurate,  and,  as  I  have  shown 
elscAvhere,^  exercise  but  little  effect  in  delaying  the 
conversion  of  the  quadriurate  into  the  biurate. 

I  wish  it  to  be  clearly  understood  that  I  do  not 
attribute  the  different  effects  of  animal  and  vege- 
table diets  on  gouty  subjects  to  the  saline  con- 
stituents alone.  I  think,  however,  that  the  results 
of  these  experiments  clearly  show  that  it  is  to  the 
different  mineral  constituents  of  animal  and  vege- 
table foods,  and  to  the  different  physical  effects 
they  exercise  on  the  quadriurate  and  biurate,  that 
we  must  look  for  a  partial  and  perhaps  a  main 
explanation  of  the  known  facts  that  an  excessive 

♦   The  Laiirt,  April  17th,  18'.»7,  p.  1074. 


Results  of  Exp/cr/mexts.  173 

diet  of  the  one  tends  to  produce  gout  and  of  the 
other  tends  to  retard  it.  • 

A  reference  to  some  of  the  tables  previous!}' 
o-iven  will  show  that  certain  veo'etables  stand  out 
prominently  with  regard  to  the  effect  exercised  by 
their  mineral  constituents  both  in  retarding  the 
conversion  of  the  sodium  quadriurate  into  the 
biurate,  and  in  increasing  the  solubility  of  the 
latter.  These  vegetables  are  spinach,  Brussels 
sprouts,  French  beans,  winter  cabbage,  Savoy 
cabbage,  turnip-tops,  turnips,  and  celery.  These 
are  the  vegetables  which  I  consider  are  likely  to 
prove  most  beneficial  to  gouty  subjects.  Of  these, 
in  so  far  as  the  effects  produced  by  their  mineral 
constituents  are  concerned,  spinach  occupies  the 
first  place,  both  as  regards  inhibiting  the  decom- 
position of  the  quadriurate  and  increasing  the 
solubility  of  the  biurate.  Spinach  has  the  further 
advantage  of  being  extremely  rich  in  mineral  con- 
stituents, since  it  contains  16'27  percent,  of  mineral 
matter  as  compared  w^ith  8-50,  which  is  the  average 
percentage  of  the  mineral  constituents  of  all  the 
vegetables  experimented  with.  It  may  be  urged 
that  a  drawback  to  the  employment  of  spinach  is 
that  it  cannot  be  obtained  fresh  throuo-hout  the 
year.  Very  excellent  spinach  is,  however,  now 
obtainable  in  the  desiccated  and  compressed  state, 
and  when  cooked  naakes  a  dish  which  is  practically 
indistinguishable  from  the  fresh  vegetable. 

Owing  to  the  undoubted  action  which  I  have 
shown  the   mineral  constituents   of  several  ves'e- 

CT 

tables  possess  in  delaying  the  conversion  of  sodium 


1/4 


A  UTHOR  's  Inves  tig  a  tions. 


quadriurate  into  biurate,  and  in  increasing  the 
solubility  of  the  latter,  it  is  possible  that  a  table 
salt  composed  of  vegetable  ashes  might  prove 
advantageous  to  the  gouty.  Sir  W.  Koberts  has 
sho^vn  that  small  quantities  of  sodium  chloride 
introduced  into  blood  serum  containing  quadri- 
urate in  solution  always  appreciably  hastened  the 
formation  and  precipitation  of  the  biurate.  In 
addition,  sodium  chloride  very  considerably  dimin- 
ishes the  solubility  of  sodium  biurate,  while  the 
mineral  constituents  of  vegetables  increase  it.  This 
is  well  shown  in  Table  XLIIL,  representing  the 
comparative  effects  of  Ol  per  cent,  solutions,  respect- 
ively, of  sodium  chloride  and  of  the  mineral  constitu- 
ents of  vegetables  on  the  solubility  of  sodium  biurate. 

TABLE    XLIII. 
Shoiving  the  comparative  effects  of  0\  per  cent,  solutions  respectively 
of  sodium   chloride  and  of  the  mineral  constituents  of  various 
vegetables  on  the  solubility  of  sodium  biurate. 


Solvent. 

Sodium 
disso' 

biurate 
ved. 

Water 

1-10  per  1,000 

Water  containin<5  :- 

— 

01 

per 

cent 

.  of  sodium  chloride 

0-4o 

)) 

spinach  ash  . . . 

1-90 

)i 

Brussels  sprouts 

ash 

1-62 

>» 

Savoy  cabbage 

)5 

1-57 

)) 

French  beans 

,, 

1-56 

>» 

lettuce 

?5 

1-53 

>» 

potato 

,, 

1-47 

>» 

beetroot 

J) 

1-45 

»» 

carrot 

„ 

1-45 

j> 

asparagus 

,, 

1-45 

» 

celery- 

■)■> 

1-44 

>> 

turnip 

>> 

1-42 

>» 

turnip  tops 

J) 

1-42 

)) 

cauliflower 

)?                        ... 

1-34 

>» 

cabbage 

,, 

1-31 

»> 

senkale 

,) 

1-23 

>) 

»' 

green  peas 

n 

110 

V 

Use  of  Vegetables.  175 

This  table  shows  the  great  advantage  that  the 
mineral  constituents  of  vegetables  possess  over 
common  salt  as  regards  their  solvent  effect  on 
sodium  biurate.  I  have  been  able  to  calculate  that 
with  the  moderately  free  use  of  vegetables,  espe- 
cially if  supplemented  by  the  use  of  a  table  salt 
prepared  from  vegetables,  it  is  quite  possible  to 
introduce  more  than  01  per  cent,  of  the  mineral 
constituents  of  vegetables  into  the  fluids  of  the 
body. 


176 


CHAPTER   XIII. 

Reasons  for  believing  the  treatment  of  gout  hij  alkalies  to 
he  erroneous — Experimental  investiyation  of  the 
value  of  the  treatmetit  of  gout  hg  the  various 
alkalies,  bg  j^ip^raziiie,  and  bg  lysidine — Reasons 
for  believing  the  treatment  of  gout  bg  salicylates  to 
be  erroneous — Experimental  investigation  of  the 
value  of  the  treatment  of  gout  by  salicylates — 
General  conclusions. 

For  a  considerable  period  of  tiaie  two  methods 
of  treatment  Avhicli  have  for  their  professed  object 
the  ehmination  of  uric  acid  from  the  system  have 
been  more  or  less  employed  by  medical  men. 
They  are  the  treatment  of  gout  by  means  of 
alkalies,  and  by  means  of  salicjdates.  These  two 
methods  of  treatment  I  consider  owe  their  popu- 
larity to  the  entirely  erroneous  supposition  that 
uric  acid  is  present  as  such  in  the  fluids  and 
deposits  of  gouty  patients,  whereas  the  uric  acid 
is  always  present  as  sodium  quadriurate  or  biurate, 
and  the  chemical  and  physical  behaviour  of  these 
substances  is  entirely  different  from  that  of  uric 
acid.  As  I  have  for  some  time  believed  that  both 
these  methods  ol  treatment  are  wrong  in  principle 
and  action  I  thought  it  expedient  to  submit  the 
matter  to  experimental  investigation. 


Experiments  with  Alkalies.  177 

lleasoxs  for  uelieving  the  treatment  of  gout 
by  alkalies  'jy)  re  erroneous. 

The  plea  for  the  treatment  of  gout  by  means  of 
alkalies  is  mainly  based  on  the  following  assump- 
tions :  (1)  That  uric  acid  is  present  in  the  blood 
and  tissues,  and  is  rendered  soluble  by  the  ad- 
ministration of  alkalies;  (2)  that  the  biurate  de- 
posited in  joints  is  rendered  soluble  by  means  of 
alkalies,  and  (3)  that  there  is  a  general  acidity 
of  the  system  which  is  neutralised  and  removed 
by  alkalies.  It  will  be  seen  that  these  assump- 
tions do  not  stand  the  test  of  experimental 
inquiry.  With  regard  to  the  first  assumption, 
it  is  now  well  known  that  in  gouty  subjects  uric 
acid  is  never  present  as  such  in  the  blood  and 
tissues,  but  is  always  combined  with  sodium  as 
the  quadriurate  or  biurate.  The  only  way  in 
which  alkalies  could  beneficially  affect  the  quad- 
riurate would  be  to  delay  its  conversion  into  the 
biurate.  In  order  to  test  this  point,  I  conducted  a 
series  of  experiments  so  as  to  ascertain  the  effect 
of  artificial  blood  serum,  to  which  different  alkalies 
had  been  added,  on  the  decomposition  of  sodium 
quadriurate.  In  all  the  experiments  the  artificial 
blood  serum  employed  was  Sir  William  Roberts's 
standard  solution  (.see  p.  87).  This  was  employed 
instead  of  blood  serum  in  order  to  obviate  the 
objections  that  have  been  raised  to  the  use  of 
blood  serum  in  such  experiments,  viz.,  the  tendency 
to  variation  in  its  alkalinity.     Moreover,  as  shown 

M 


1/8  Author's  Investigations. 

by  Sir  William  Roberts,  this  standard  solution 
reacts  with  uric  acid  and  with  the  quadriurates 
and  biurates  in  the  same  manner  as  blood  serum 
itself. 

OBJECTS    OF    COXD'JCTING    THE    EXPERIMENTS   WFTH 
SODIUM    QUADRIURATE. 

These  experiments  were  undertaken  in  order  to 
ascertain  w^hether  any  of  the  drugs,  ordinarily  em- 
ployed in  the  alkaline  treatment  of  gout,  possess 
any  power,  when  introduced  into  the  circulation,  of 
restraining  the  precipitation  of  sodium  biurate  from 
the  quadriurate  contained  in  the  blood.  Such  ex- 
periments would  show  whether  any  such  drugs 
would  be  of  use  either  in  delaying  or  partially 
arresting  an  attack  of  gout,  or  in  lessening  the 
formation  of  gouty  deposits. 

When  sodium  quadriurate  is  mixed  with  water 
it  is  decomposed  into  a  uric  acid  moiety  and  a 
sodium  biurate  moiety,  the  uric  acid  appearing, 
immediately  it  is  set  free,  in  the  form  of  ovoid 
or  spindle-shaped  crystals.  These  crystals  appear 
in  a  very  short  time  after  the  contact  of  the  quadri- 
urate with  water — generally  in  from  one  to  five 
minutes — whilst  the  sodium  biurate  passes  into  the 
gelatinous  form,  which,  if  sufficient  water  be  pre- 
sent, is  dissolved.  If,  instead  of  water,  an  alkaline 
medium  be  employed  to  decompose  the  quadriurate, 
such  as  blood  serum,  or  artificial  blood  serum,  at 
the  temperature  of  the  human  body,  then  as  long 
as  free  alkaline  carbonate  is  present  the  uric  acid 
moiety  of  the  quadriurate,  instead  of  crystallising 


Experiments  with  Alkalies.  179 

out  as  uric  acid,  unites  with  the  sodium  carbonate 
to  form  sodium  biurate,  which  first  assumes  the 
amorphous  form.  After  a  time  this  amorphous 
biurate  becomes  gradually  converted  into  the 
needles  of  the  crystalline  biurate.  The  time, 
therefore,  that  elapses  between  the  saturation  of 
the  blood  serum  with  sodium  quadriurate,  and  the 
first  appearance  of  needle-shaped  crystals  of  sodium 
biurate  represents  the  inhibitory  influence  of  the 
medium  on  the  crystalline  precipitation  of  sodium 
biurate.  The  experiments  to  ascertain  the  effect 
of  drugs  employed  in  the  alkaline  treatment  of 
gout  were  conducted  in  the  following  manner. 

METHOD    OF    COXDUCTIXG    THE     EXPERIMENTS    WITH 
SODIUM   QUADRIURATE. 

Ten  milligrammes  of  sodium  quadriurate  were 
well  rubbed  with  ten  drops  of  a  01  per  cent,  solu- 
tion of  the  druo-  in  artificial  blood  serum,  and  the 
mixture  was  then  placed  in  a  small  corked  tube 
and  kept  at  a  100'  F.  Every  half-hour  a  small 
quantity  of  the  mixture  was  removed  and  examined 
under  a  high  power  of  the  microscope,  and  the 
time  at  which  crystals  of  the  sodium  biurate  first 
appeared  was  noted.  A  similar  experiment,  for 
purposes  of  comparison,  was  made  with  the  quadri- 
urate and  artificial  blood  serum  alone.  I  experi- 
mented separately  in  this  way  with  potassium 
bicarbonate,  potassium  citrate,  lithium  carbonate, 
lithium  citrate,  sodium  bicarbonate,  sodium  phos- 
phate, piperazine,  and  lysidine.  The  results  are 
shown  in  the  following  table  : — 


i8o 


A  UTHOR  'S    In  VES  tig  a  TIONS. 


TABLE    XLIV. 

Showing  the  'ui^ffnencc  exerted  on  the  decoivposition  of  sodium  quadrl- 
iirate  by  artificial  blood  serum  alone,  and  by  artificial  blood  serum 
coutaininj  O'l  per  cent,  of  various  drugs  in  solution. 


Sodimn  bi urate  cr.vs- 

iSdlveiit. 

tals  appeared  after 
the  lapse  of — 

Artificial  blood  serum     ...         ...         

2  hours 

J>                                   55 

containing  01  per  cent,  of 

potassium  bicarbonate 

>» 

5>                                   5) 

containing  O'l  per  cent,  of 

potassium  citrate 

55 

55                                   J» 

containing  01  percent,  of 

lithium  carbonate    ... 

M 

!5                                   n 

containing  0*1  per  cent,  of 

lithium  citrate 

ij 

J5                         iy 

containing  O'l  per  cent,  of 

sodium  bicarbonate . . . 

>> 

J5                                   ?' 

containing  0- 1  per  cent,  of 

sodium  phosphate    .. 

M 

?5                                   ?> 

containing  0"1  per  cent,  of 

pipcrazine 

5) 

,, 

containing  O'l  percent,  of 

lysidine 

11 

These  results  show  that  none  of  the  drugs  men- 
tioned in  the  table  exercise  the  slightest  effect  in 
delaying  the  conversion  of  the  quadriurate  into  the 
l)iurate,  even  when  present  in  far  larger  proportions 
than  could  possibly  be  introduced  into  the  blood 
by  the  medicinal  administration  of  the  drugs."^ 
Therefore  it  appears  that  the  treatment  of  gout  by 
alkalies  and  saUs  of  the  alkalies  does  not  delay  the 
conversion  of  the  quadriurate  into  the  biurate. 

DOES     THE      TREATMENT      OF      GOUT      BY     ALKALIES 
INCREASE    THE    SOLUBILITY    OF    SODIUM    BIURATE  ? 

With  regard  to  the  second  assumption,  that  the 
administration  of  alkalies  increases  the  solubility  of 

*  In  order  to  have  0-1  jDer  cent,  of  any  drug  in  the  blood,  it 
would  be  necessary  to  introduce  100  grains  of  that  drug  at  once 
into  the  circulation  of  an  adult  man  of  average  weight. 


ExPERfMEXTS    WITH   A  LK A  LIES.  l8[ 

the  bi urate  deposited  in  the  joints  and  tissues, 
Sir  William  Roberts'^  has  shown  that  sodium  bi- 
carbonate and  sodium  phosphate  diminish  the 
sohibiHty  of  sodium  biurate,  while  potassium  bi- 
carbonate exercises  no  influence  whatever  on  its 
solubility.  He  fails  to  find  any  direct  object  in 
the  administration  of  alkalies  for  gout,  and  he  has 
seen  gouty  attacks  recur  with  full  severity  when 
the  urine  has  been  for  a  lono^  time  maintained 
persistently  alkaline  by  the  administration  of 
bicarbonate  and  citrate  of  potassium.  That  the 
administration  of  alkalies  might  increase  the  solu- 
bility of  the  biurate  appeared  at  one  time  to  be 
probable  from  the  results  of  some  experiments 
performed  by  Sir  i\.lfred  Garrod.  He  immersed 
small  pieces  of  cartilage  infiltrated  with  sodium 
biurate  for  forty-eight  hours  in  aqueous  solutions 
of  the  carbonates  of  lithium,  potassium,  and  sodium 
respectively.  At  the  end  of  that  time  he  foitnd 
that  the  cartilage  immersed  in  the  lithium  solution 
was  restored  to  its  natural  condition ;  that  in  the 
potassium  solution  was  much  acted  upon,  wdiile 
that  in  the  sodium  solution  appeared  to  be  un- 
altered. These  results  are  somewhat  in  opposition 
to  those  of  Sir  AVilliam  Roberts,  and  as  neither  the 
experiments  of  Sir  Alfred  Garrod  nor  those  of  Sir 
William  Roberts  represent  the  conditions  under 
which  alkalies,  when  introduced  into  the  circula- 
tion, would  act  on  sodium  biurate,  I  thought  it 
desirable  to  re-investigate  the  subject,  as  far  as 
possible  under  such  conditions. 

*  The  Croonian  Lecture?,  1892. 


1 82  Author's  Investigations. 

investigation  of  the  effects  of  various 
alkaline  drugs  on  the  solubility  of 
sodium    biurate. 

These  experiments  were  undertaken  in  order  to 
compare  the  sokibiHty  at  100'  F.  of  sodium  biurate 
in  artificial  blood  serum,  and  in  artificial  blood 
serum  containing  different  proportions  of  the 
various  drugs.  The  experiments  were  carried  out 
in  a  similar  manner  to  that  described  on  pp.  137, 
138.  I  experimented  separately  with  the  following- 
drugs — potassium  bicarbonate,  potassium  citrate, 
lithium  carbonate,  lithium  citrate,  sodium  bicar- 
bonate, sodium  phosphate,  piperazine,  and  Ijsidine. 
Much  greater  proportions  of  the  drugs  were  em- 
ployed than  could  possibly  be  introduced  into  the 
blood  by  medicinal  administratioix  The  results 
are  shown  in  the  following  tables :-  — 

TABLE    XLY. 

Showing  the  soluhUity  at  100°  F.  of  sodium  biurate  in  artifcial  blood 
serum  alone,  and  in  artifcial  blood  serum  containing  different 
proportions  of  potassium  bicarbonate. 


Solvent.  Sodium  biurate 

I  ULssolved. 


Artificial  Mood  serum  ■      0-11  per  1,000 

Artificial  blood  serum  containing  001  per     | 

cent,  of  potassium  bicarbonate    ...  ...  010         ,, 

Artificial  blood  serum  containing  010  per 

cent,  of  potassium  bicaiboiiito    ...  ...  010         ,, 

Artificial  blood  serum  containing  0"20  per 

cent,  of  potassium  bicarbonate    ...  ...  0*11         „ 


These  results  show  that  potassium  bicarbonate 


Experiments  with  Alkalies. 


183 


would   not    in   tlie  slightest   degree    increase   the 
solvent  j)ower  of  the  blood  for  gouty  deposits. 

TABLE    XLYI. 

Shoicing  the  soJiihility  at  100°  F.  of  sodluin  biurate  in  artificial  blood 
serum  alone,  and  in  artificial  blood  serum  containing  different 
proportions  of  potassium  citrate. 


Solvent. 


Artificial  blood  serum 

Artificial  blood  serum  containing-  O'Ol  per 

cent,  of  potassium  citrate  .. 
Artificial  blood  serum  containing  O'lO  per 

cent,  of  potassium  citrate.. 
Artificial  blood  serum  containing  0"20  per 

cent,  of  potassium  citrate... 


Sodium  biurate 
dissolved. 


0-11  per  1,0C0 
0-10  „ 

0-10         „ 
Oil 


These  results  show  that  potassium  citrate  would 
not  in  the  slightest  degree  increase  the  solvent  power 
of  the  blood  for  gouty  deposits. 

TABLE    XLYII. 

Showing  the  solubility  at  100°  F.  of  sodium  liura^e  in  artificial  blood 
serum  alone,  and  in  artificial  blood  serum  containing  different 
proportions  of  lithium  carbonate. 


Solvent. 


Artificial  blood  sei'um 

Artificial  blood  serum  containing  0-005  per 

cent,  of  lithium  carbonate 
Ai'tificial  blood  serum  containing  O'Ol  per 

cent,  of  lithium  carbonate 
Artificial  blood  serum'  containing  O'lO  per 

cent,  of  lithium  carbonate 


Sodium  l)i urate 
dissolved. 


0-11  per  1,000 

0-11 

0-11 

0-15 


These  results  show  that  lithium  carbonate  would 
not  in  the  slio-htest  deo'ree  increase  the  solvent 
power  of  the  blood  for  gouty  deposits,  even  when 
present  in   far  larger  proportions  than  could   be 


1 84 


A  UTHOR  'S    Ix  I  ^ES  TIG  A  TIOXS. 


introduced  into  the  blood  by  medicinal  adminis- 
tration. Lithium  salts  are  usually  given  in  doses  of 
one  to  five  grains  three  times  a  day,  whereas  to 
get  001  per  cent,  of  a  lithium  salt  into  the  blood  it 
would  be  necessary  to  introduce  10  grains  of  the 
salt  at  once  into  the  circulation  of  an  adult  man  of 
average  weight. 

TABLE    XLVIII. 

Showing  the  solubility  at  100^  F.  of  sodium  biurate  in  artificial  blood 
serum  alone,  and  in  artificial  blood  scrum  containing  different 
proportions  of  lithium  citrate. 


Solvent. 

Sodium  biurate 
dissolved. 

Artificial  blood  serum 

0-11  per  1,000 

Artificial  blood  serum  containing  0-005 

per 

cent,  of  lithium  citrate     ... 

0-11 

Artificial  blood  serum  containing  0-01 

per 

cent,  of  lithium  citrate 

0-11 

Artificial  blood  serum  containing  0  10 

l)er 

cent,  of  lithium  citrate 

... 

Oil          „ 

These  results  show  that  lithium  citrate  would 
not  in  the  slightest  degree  increase  the  solvent 
power  of  the  blood  for  gouty  deposits. 

TABLE    XLIX. 

Showing  the  solubility  at  100°  F.  of  sodium  biurate  in  artificial  blood 
serum  alone,  and  in  artificial  blood  serum  containing  different 
proportions  of  sodium  bicarbonate. 


Solvent. 


Artificial  blood  serum 

Artificial  blood  serum  containing  O'Cl  per 

cent,  of  sodium  bicarbonate 
Artificial  blood  serum  containing  010  per 

cent   of  sodium  bicarbonate 
Artificial  blood  serum  containing  ()-20   per 

cent,  of  sodium  T)icarbonato 


Sodium  biurate 
di.s.solved. 


Oil  per  1,000 

0-10 

003 

OOS 


Experiments  with  Piperazixe. 


i8i 


These  results  show  that  sodium  bicarbonate 
would  sKghtly  decrease  the  solvent  power  of  the 
blood  for  gouty  deposits. 


TABLE   L. 

iShoiCing  the  solubility  at  100'  F.  of  sodium  hinratc  in  artificial  blood 
sennn  alone,  and  in  artificial  blood  serum  containing  different 
proportions  of  sodium  phosphate. 


.S-lveut. 


Artificial  blood  serum 

Artificial  blood  serum  containing  O'Ol  per 

cent,  of  sodium  phosphate 
x\rtiticial  blood  serum  containing  0-10  per 

cent,  of  sodium  phosphate 
Artificial  blood  serum  containing  0-20  per 

cent,  of  sodium  phosphate 


Sodimii  biiirate 
dissolved. 


O-Il  per  1,000 

0-11 

0-11 

Oil 


These  results  show  that  sodium  phosphate 
would  not  in  the  slightest  degree  increase  the 
solvent  power  of  the  blood  for  gouty  deposits. 


TABLE    LI. 

Showing  the  solubility  at  100'  F.  of  sodium  biurate  in  artificial  blood 
serum  alone,  and  in  artificial  blood  serum  containing  different 
proportions  of  piperazine . 


Solvent. 


Artificial  blood  serum 

Artificial  blood  serum  containing  0-01  pe 

cent,  of  piperazine... 
Artificial  blood  serum  containing  O'lO  per 

cent,  of  piperazine... 
Artificial  blood  serum  containing  0"20  per 

cent,  of  i^iperazine... 


Sodium  biurate 
dissolved. 


0-11  per  1,000 
0-09         „     . 

o-u 

0-13 


These  results  show  that  piperazine  would  not 


i86  Author's  Investigations. 

in  the  slightest  degree  increase  the  solvent  power 
of  the  blood  for  gouty  deposits,  even  when  present 
in  far  larger  portions  than  could  be '  introduced 
into  the  blood  by  medicinal  administration.  Piper- 
azine  is  usually  given  in  doses  of  five  grains  three 
times  a  day,  whereas  to  get  0*10  per  cent,  of  piper- 
azine  into  the  blood  it  would  be  necessary  to  in- 
troduce 100  grains  of  the  drug  at  once  into  the 
circulation  of  an  adult  man  of  average  weight. 

TABLE    LII. 

Showing  the  solnhiUty  at  100°  F.  of  sodium  binrate  in  artificial  blood 
serum  alone,  and  in  artificial  blood  serum  contai)iing  different 
proportions  of  hjsidine. 


Solvent. 


Artificial  blood  serum 

Artificial  hlood  serum  containing  O'Ol  per 

cent,  of  lysidine 
Artificial  blood  serum  containing  0  10  per 

cent,  of  lysidine     ... 
Artificial  blood  serum  containing  0-20  per 

cent,  of  lysidine     ... 


S<jiliuin  l)iurate 
elissolved. 


0-11  per  1,000 
0-09         „ 
0-10 
010 


These  results  show  that  lysidine  would  not  in  the 
slightest  degree  increase  the  solvent  power  of  the 
blood  for  gouty  deposits,  even  when  present  in  far 
larger  proportions  than  could  be  introduced  into 
the  blood  by  medicinal  administration.  Lysidine  is 
mven  in  doses  of  from  30  to  120  grains  three  tunes 
a  day,  whereas  to  get  020  per  cent,  of  lysidine  into 
the  blood  it  would  be  necessary  to  introduce  200 
grains  of  the  druof  at  once  into  the  circulation  of  an 
-.dult  man  of  average  weight. 


Experiments  with  Gouty  Deposits.     187 

further  experiments  as  to  the  influence  of 
potassium  and  lithium  salts  on  the  solv- 
ency   of    gouty   deposits. 

As  it  appeared  to  me  tliat  the  experiments  of  Sir 
Alfred  Garrod,  previously  referred  to  [see  p.  181),  as 
to  the  solvent  effect  of  potassium  bicarbonate  and 
lithium  carbonate  on  gouty  deposits,  were  scarcely 
comparable  with  what  occurs  when  those  drugs 
are  acting  via  the  blood  and  other  fluids  of 
the  body,  I  thought  it  desirable  to  repeat  the 
experiments  under  different  conditions.  I  there- 
fore investigated  the  solvent  action  on  gouty 
deposits  of  artificial  blood  serum  impregnated 
w^ith  quantities  of  potassium  bicarbonate  and 
lithium  carbonate  respectively ;  the  quantities  of 
the  drugs  used  were  as  nearly  as  possible  equal 
to  those  which  would  be  present  in  the  fluids  of 
the  human  body  when  full  doses  are  being  admin- 
istered. The  artificial  blood  serum  impregnated 
with  potassium  bicarbonate  contained  0-01  per 
cent,  of  that  druof.  The  artificial  blood  serum 
impregnated  Avith  lithium  carbonate  contained 
O'OOlo  per  cent,  of  that  drug.  The  experiments 
w^ere  carried  out  in  the  following  manner. 

METHOD  OF  ASCERTAINING  THE  SOLVENT  EFFECTS  OF 
POTASSIUM  BICARBONATE  AND  LITHIUM  CAR- 
BONATE  ON    GOUTY   DEPOSITS. 

A  piece  of  cartilage  well  and  uniformly  infil- 
trated   with    sodium     biurate,    which    had    been 


1 88  Author's  Investigations, 

removed  from  a  gouty  joint  at  a  post-mortem 
examination,  was  divided  into  three  equal  pieces. 
One  piece  was  suspended  in  a  bottle  containing 
100  c.c.  of  artificial  blood  serum,  the  second  piece 
in  a  bottle  containingf  100  c.c.  of  artificial  blood 
serum  impregnated  with  potassium  bicarbonate' 
and  the  third  piece  in  a  bottle  containing  100  c.c. 
of  artificial  blood  serum  impregnated  with  lithium 
carbonate.  The  bottles  with  their  contents  were 
kept  throughout  the  experiments  at  the  blood  heat, 
and  every  twenty-four  hours  fresh  supplies  of  fluid 
were  introduced,  so  that  the  first  piece  of  cartilage 
was  constantly  bathed  in  artificial  blood  serum  at 
the  blood  heat,  the  second  piece  in  artificial  blood 
serum  impregnated  with  potassium  bicarbonate, 
and  the  third  piece  in  artificial  blood  serum  im- 
pregnated with  lithium  carbonate.  By  this  method 
of  procedure  it  was  considered,  as  regards  any 
solvent  effect  that  the  drugs  might  exert  on  the 
gouty  deposit,  that  the  results  would  be  fairly 
comparable  with  what  occurs  when  potassium  or 
lithium  salts  are  medicinally  administered.  The 
pieces  of  cartilage  were  removed  every  twenty-four 
hours  and  examined  by  means  of  a  lens,  and  the 
experiments  were  continued  until  all  the  sodium 
biurate  was  dissolved  out  of  the  cartilage.  The 
solution  of  the  sodium  biurate  from  the  cartilage 
proceeded  at  the  same  pace  in  the  three  pieces,  and 
was  in  no  way  accelerated  by  the  presence  of  the 
potassium  bicarbonate  or  the  lithium  carbonate. 
The  sodium  biurate  was  completely  dissolved  from 
the  three  pieces  of  cartilage  on  the  fifteenth  day. 


Alkalies  and  Gout.  189 

These  experiments  indicate  that  the  quantities 
of  potassiiiiD   bicarbonate   and   lithium   carbonate 
that  could,  by  ordinary  dosage,  be  introduced  into 
the  fluids  of  the  body  can  exercise  no  influence  on 
the   solvency   of  gouty   deposits,   and    the   results 
obtained  support  the  view  of  Sir  William  Roberts 
that  potassium  bicarbonate  and  lithium  carbonate 
exercise  no  influence  on  the  solubility  of  sodium 
biurate.     The  net  result  of  all  these  experiments 
is  that  the  treatment  of  gout  by  alkalies  or   by 
piperazine  or  lysidine  does  not  increase  the  solu- 
bility of  the  biurate  deposited  in   the  joints  and 
tissues.     Levison^  holds  very  similar  opinions  with 
regard   to    the   alkaline    treatment   of  gout.      He 
considers  that  the  administration  of  the  ordinary 
akalies,  of  lithium  salts,  or  of  piperazine  with  the 
object   of  either  dissolving   sodium   biurate  or   of 
preventing  its  deposition  is  decidedly  useless.      He 
also  found  that   the  administration  of  piperazine 
exerts  no  influence  upon  the  amount  of  uric  acid 
excreted.     Sir  William  Roberts  f  does  not  find  any 
direct  object  in  the  administration  of  alkalies  for 
gout ;  he   has  seen  gouty  attacks  recur  with  full 
severity  when  the  urine  has  been  for  a  long  time 
maintained  persistently  alkaline   by  the   adminis- 
tration    of    potassium    bicarbonate    and     citrate. 
Dr.  J.  Fawcett,i  ^^  the  result  o(  his  investigations 
on  the  treatment  of  gout  by  piperazine,  arrives  at 
an   unfavourable  conclusion   as    to   its  efficacy  in 

*  "  The  Uric  Acid  Diathesis,"  1891. 
t  The  Croonian  Lectures,  1892, 
X  Guy's  Hospital  Reports,  1895. 


190  Author's  Investigations. 

gout.  He  found  tliat  in  acute  cases  it  did  not 
relieve  the  pain,  nor  was  there  any  constant  in- 
crease in  the  excretion  of  uric  acid  under  its  use. 
Mordhorst  "^  also  considers  that  piperazine  and 
Ijsidine  are  useless  in  the  treatment  of  gout. 

A   GENERAL   ACIDITY   OF   THE    SYSTEM   NOT 
ASSOCIATED   WITH   GOUT. 

The  third  assumption  {see  p.  177),  that  in  con- 
nection with  gout  there  is  a  general  acidity  of  the 
system  which  causes  a  diminished  alkalinity  of  the 
blood,  is  opposed  to  the  results  of  recent  in- 
vestigations on  the  subject.  The  experiments  of 
Klemperer  and  my  own  experiments  {see  p.  130) 
show  that  the  alkalinity  of  the  blood  of  gout  is  but 
very  little,  if  at  all,  diminished,  and  that  corre- 
sponding variations  in  the  alkalinity  of  the  blood 
may  frequently  be  met  with  in  healthy  individuals. 
Moreover,  the  experiments  described  on  pp.  131-lo9 
demonstrate  that  a  diminution  in  the  alkalinity  of 
blood  serum  containing  uric  acid  in  solution  does 
not  facilitate  the  deposition  of  sodium  biurate  from 
it,  nor  does  a  diminution  in  the  alkalinity  of  blood 
serum  diminish  its  solvent  power  for  sodium 
biurate.  It  appears  therefore  that  there  is  no 
ground  whatever  for  the  assumption  that  the 
treatment  of  gout  by  alkalies  tends  to  neutralise 
a  so-called  general  acidity  of  the  S3^stem,  and  so 
renders  the  blood  a  better  solvent  of  gouty 
deposits. 

♦  Therap,  Mo7iats.,  x.,  1896. 


Alkalinity  of  Blood.  191 

no  relatioxship  between  the  acidity   of  the 
urine  and  the  akalinity  of  the  blood. 

The  idea  that  a  general  acidity  of  the  system  is 
associated  with  gout  has,  in  my  opinion,  arisen 
from  observations  of  the  fact  that  the  urine  of  gouty 
patients  is  acid.  These  observations  are  generally 
made  on  small  samples  of  the  urine,  although  when 
the  total  acidity  of  the  urine  for  the  twenty-four 
hours  is  determined,  it  is  frequently  found  to  be 
below  that  of  the  normal  acid  output  in  the  urine 
for  that  period  of  time.  It  is  certain  that  the 
erroneous  assumption  has  been  made  by  some 
TVTiters  that  variations  in  the  acidity  of  the  urine 
can  be  taken  as  a  gauge  of  corresponding  variations 
in  the  alkalinity  of  the  blood,  and  that  therefore 
a  fall  of  acidity  in  the  urine  means  an  increased 
alkalinity  of  the  blood,  and  vice  versa.  That  this 
assumption  is  quite  wrong  is  shown  by  reference  to 
the  following  table  (Table  LIIL),  in  which  are 
arranged  side  by  side  the  determinations  that  I 
made  on  the  same  days  of  the  alkalinity  of  the 
blood  and  of  the  total  acidity  of  the  urine  for  each 
twenty-four  hours  of  an  adult  patient  suffering 
from  subacute  o-out.  The  total  aciditv  of  the 
urine  was  determined  by  collecting  the  whole  of 
the  urine  for  the  twenty-four  hours,  and  then 
titrating  a  portion  of  the  urine  by  the  process 
described  by  Lepinois."^  The  estimations  were 
made  mostly  on  alternate  days  throughout  the 
duration  of  the  attack. 

*  /.  Fharm.,  1896  (6),  iii.,  8—16. 


192 


A  UTHOR  'S    Ix  VES  TIG  A  TIONS. 


TABLE    LIII. 

Shoiv'nig  the  ahsence  of  autj  constant  relationshi})  between  the  alkriiinltt/ 
of  the  blood  and  the  acidify  of  the  urine  of  a  patient  during  an 
attack  of  subacute  gout. 


Dates  of 
determinations. 

Alkalinity  repre-sented    as 
percentage   of  anhydrou.s 
sodium  rarbonate  present 
in  the  blood. 

Acidity   of   total   urine   fnr 
the  24  hours  reckoned  as 
grammes  of  hydrochloric 
acid. 

Feb. 

4th. 

0-167 

1-392 

6th. 

0-167 

0-953 

8th. 
lOih. 

0-167 
0-1.-6 

1-096 
1-374 

12th. 
loth. 
17th. 

0-167 
0-158 
0-lo8 

1-583 
1-529 
1-629 

19th. 

0-167 

1-581 

22nd. 
24th. 

0180 
0  173 

1-602 
Alkaline 

2C.th. 
28th. 

0-161 
0  179 

Alkaline 
0-608 

:\Iar 

2nd. 

0167 

0-622 

This  table  shows  that  no  constant  relationship 
existed  in  this  case  of  gout  between  the  alkalinity 


.i 

A 

s. 

/ 

^ 

y 

y 

^^ 

■> 

/ 

^ 

v 

/ 

v^ 

y 

B 

/ 
X 
/ 

■*  * , 

'" 

"  "' 

'^ 

1 
I 

\ 
\ 
^ 

\ 
\ 

"" 

i 
/ 

— 

\ 

\ 
\ 

At 

fUt, 

'^aii 

^ 

p^ 

Ur 

tne 

\ 

/ 

^^^ 

^^^ 

^^* 

^^^ 

1 

1 

Diagram  showing  the  absence  of  any  constant  relationship  between 
the  alkalinity  of  the  blood  and  the  acidity  of  the  urine  of  a 
patient  during  an  attack  of  subacute  gout. 

A,  Alkalinity  of  blood  ;  B,  acidity  of  urine. 


Salicylates  and  Gout.  193 

of  the  blood  and  the  acidity  of  the  urine,  and 
moreover  that  on  those  days  when,  owing  to 
treatment  with  citrate  of  potassium  which  was 
administered  from  February  1.9th  to  28th,  the  urine 
remained  alkaline,  there  was  no  corresponding  rise 
in  the  alkalinitj^  oi  the  blood. 

These  determinations  of  the  alkalinity  of  the 
blood  and  the  acidity  of  the  urine  of  this  case  of 
subacute  gout  are  shown  in  curves  in  the  diagram  on 
p.  192,  a  glance  at  which  at  once  demonstrates  that 
no  constant  relationship  existed  between  the  alka- 
linity of  the  blood  and  the  acidity  of  the  urine. 

REA.SOXS    FOR   BELIEVIXG   THE   TREATMENT    OF    GOUT 
BY   SALICYLATES   TO    BE    ERRONEOUS. 

Just  as  the  treatment  of  gout  by  means  of 
alkalies  is  based  on  the  entirely  erroneous  supposi- 
tion that  uric  acid  is  present  as  such  in  the  fluids 
and  deposits  of  gouty  patients,  so  the  main  reason 
for  giving  a  salicylate  in  gout  is  based  on  the 
assumption  that  it  unites  with  uric  acid  throughout 
the  system,  and  so  effects  its  removal  from  the 
system  and  its  elimination  in  the  urine.  That 
sodium  salicylate  does  cause  an  increased  elimina- 
tion of  uric  acid  in  the  urine,  at  all  events  in  the 
early  stages  of  its  administration,  is  undoubted. 
This  is  shown  by  the  following  daily  deter- 
minations that  I  made  of  the  total  uric  acid 
excretion  of  a  healthy  man  before,  during,  and 
after  treatment  with  sodium  salicylate.  The 
diet  was  of  the  same  nature  throughout  the 
experiment. 

N 


194 


A  uthor's  In  I  'es  tig  a  tions. 


TABLE    LIV. 

Showing  the  daily  excretion  on  successive  days  of  uric  acid  by  a 
healthy  man  before,  during,  and  after  treatment  tvith  sodium 
salicylate. 


Daily  excretinii  of  uric 
acid  in  gianunes. 

(    0-547 

Before  taking  salicylate     J    0-589 

(    0-731 

Average 0-622 

,     0-852 
Fifteen  grains  of  sodium  salicylate  taken      \    0942 

three  times  a  day..           ...         i    0-826 

I    0-784 

Average     ...         0851 

Salicylate  left  off 

Average 

f  0-340 
0-581 
0-543 
0-677 

^  0-686 

0-565 

That  this  increased  elimination  of  uric  acid  is 
due,  however,  to  the  removal  of  ready-formed  uric 
acid  stored  in  the  system  is,  in  my  opinion,  in- 
correct. In  the  first  place  it  must  be  remembered 
that  any  uric  acid  deposited  in  any  of  the  organs  or 
tissues  of  gouty  subjects  is  deposited  in  the  form  of 
sodium  biurate,  and  the  results  of  the  following 
experiments  show  that  artificial  blood  serum  con- 
taining sodium  salicylate,  in  much  greater  pro- 
portions than  could  be  introduced  into  the  blood 
by  the  medicinal  administration  of  the  drug,  has 
not  the  sliofhtest  increased  solvent  effect  on  the 
biurate. 


Salicylates  and  Gout.  195 

TABLE    LV. 

Showing  the  soluhility  at  100^  F.  of  sodium  biurate  in  artijicial 
blood  serum  alone,  and  in  artijicial  blood  serum  containiny 
diffi  rent  proportions  of  sodium  salirylate. 

Solvent  '         Sodium  biurate 

dissolved. 


Artificial  blood  serum  0-11  per  1,000 

Artificial  blood  serum  containing  O'OOS  per 

cent,  of  sodium  salicylate...         ...         ...  0-11         „ 

Artificial  blood  serum  containing  0  006  per 

cent,  of  sodium  salicylate...         ...         ...     i       0-11         ,, 

Artificial  blood  serum  containing  Q-Ol  per     i 

cent,  of  sodium  salicylate...         ...         ...     j       0-11         „ 

Artificial  blood  serum  containing  O'lO  jjer     ! 

cent,  of  sodium  salicylate...         ...         ...  O'll 


These  results  show  that  sodium  saHcylate  avouIcI 
not  in  the  sUghtest  degree  increase  the  solvent 
power  of  the  blood  for  gouty  deposits,  even  when 
present  in  far  larger  pro23ortions  than  could  be 
introduced  into  the  blood  by  medicinal  administra- 
tion. Sodium  salicylate  is  usually  given,  in  the 
treatment  of  gout,  in  doses  of  fifteen  to  twenty 
grains  three  times  a  day,  whereas  to  get  01  per 
cent,  of  sodium  salicylate  into  the  blood  it  would 
be  necessary  to  introduce  100  grains  of  the  drug  at 
once  into  the  circulation  of  an  adult  man  of  average 
weight.  Dr.  J.  Fawcett,"^  who  likewise  finds  that 
sodium  salicylate  produces  an  increased  uric  acid 
excretion,  considers  it  improbable  that  the  increase 
can  be  explained  by  a  mere  clearing  out  of  retained 
uric  acid. 

I  also  find  that  artificial  blood  serum  containing 
sodium  salicylate  m  far  larger  proportions  than 
could  be  introduced  into  the  blood  by  medicinal 

*  Guy's  Hospital  Eeports,  1895. 


ig6  Author's  Investigations. 

administration  has  no  effect  whatever  in  delaying 
the  conversion  of  sodium  quadriurate  into  the 
biurate,  as  is  shown  in  the  following  table : — 

TABLE    LVI. 

ShoiCDig  the  xufiuence  exerted  on  the  decompontion  of  sodinm  qual- 
riurate  by  artijicial  blood  (■erum,  and  by  artijiclal  blood  scrum 
containing  0"1  per  cent,  of  sodium  salicylate  in  solution. 


Solvent. 

Sodium  biurate  cryslals 
api>eared     after     the 
lapse  of — 

Artifioial  blood  serum 

Artificial  blood   serura  containing  0"1   per 
cent,  of  sodium  salicylate ... 

2  hours 
2  hours 

It  therefore  appears  from  the  results  of  the 
experiments  given  in  Tables  LY.  and  LYI.  that 
sodium  salicylate  has  no  direct  action  either  in 
delaying  the  decomposition  of  sodium  quadriurate 
or  in  effecting  a  solvent  action  on  deposits  of 
sodium  biurate.  The  erroneous  supposition  as  to 
salicylates  possessing  a  solvent  power  on  gouty 
deposits  probably  arose  from  the  faulty  deduction 
that  increased  elimination  of  uric  acid  in  the  urine 
after  the  administration  of  a  salicylate  was  neces- 
sarily due  to  the  solvent  effect  of  the  salicylate  on 
uratic  deposits.  The  correct  explanation  of  this 
increased  elimination  of  uric  acid  is,  I  believe,  to 
be  found  in  the  known  fact  that  salicylic  acid 
unites  readily  with  glycocine  to  form  salicyluric 
acid,  and  that  it  thus  brings  an  increased  amount 
of  glycocine  to  the  kidneys,  where  by  the  com- 
bination of  that  body  Avith  urea  an  increased 
amount  of  uric  acid  is  necessarily  formed.     Since, 


General  Conclusions.  197 

therefore,  I  believe  that  the  effect  of  a  salicylate 
is  to  increase  the  production  of  uric  acid  in  the 
kidneys  by  bringing  additional  glycocine  to  those 
organs,  I  am  of  opinion  that  salicylates  are  contra- 
indicated  in  gout,  as  increased  production  of  uric 
acid  in  kidneys  which  are  already  incapable  of 
eliminatino:  the  normal  amount  of  uric  acid  would 
lead  to  increased  absorption  of  uric  acid  into  the 
general  circulation,  and,  consequently,  to  intensifi- 
cation of  the  gouty  condition. 

GENERAL     CONCLUSIONS     DRAWN     FROM     THE 
INVESTIGATIONS. 

1.  The  alkalinity  of  the  blood  is  apparently 
not  appreciably  diminished  during  a  gouty  attack. 

2.  The  solubility  of  uric  acid  in  the  blood 
is  not  afiected  by  a  diminished  alkalinity  of  the 
blood  produced  by  the  addition  of  organic  acids. 

3.  The  deposition  of  sodium  bi urate  is  not 
accelerated  by  a  diminution  of  the  alkalinity  of  the 
blood. 

4.  An  increased  alkalinity  of  the  blood  does 
not  increase  the  solubility  of  deposits  of  sodium 
biurate. 

5.  The  gout-inducing  properties  of  certain 
wines  are  not  due  to  their  acidity.  Probably 
they  owe  their  gout-inducing  action  to  the  effect 
they  exercise  on  the  metabolism  of  the  liver. 

6.  The  solubility  of  sodium  biurate  is  markedly 
increased  by  the  presence  of  the  mineral  con- 
stituents of  most  vegetables. 

7.  The  solubility  of  sodium  biurate  is  dimin- 


i 


198  Author's  Investigations. 

ished  by  the  presence  of  the  mineral  constituents 
of  meat. 

8.  The  mineral  constituents  of  certain  vege- 
tables delay  the  conversion  of  sodium  quadriurate 
into  the  biurate. 

9.  The  vegetables  most  useful  to  gouty  sub- 
jects are  spinach,  Brussels  sprouts,  French  beans, 
winter  cabbage.  Savoy  cabbage,  turnip  tops,  turnips, 
and  celery. 

10.  The  administration  of  the  ordinary  alkahes, 
of  lithium  salts,  of  piperazine,  and  of  lysidine,  with 
the  object  of  removing  gouty  deposits,  appears  to 
be  useless. 

11.  No  general  acidity  of  the  system  is  asso- 
ciated with  gout. 

12.  xso  relationship  exists  between  the  acidity 
of  the  urine  and  the  alkalinity  of  the  blood. 

13.  The  administration  of  salicylates  with  the 
object  of  removing  gouty  deposits  appears  to  be 
useless,  and  their  employment  in  the  treatment  of 
gout  is  contra-indicated. 


199 


lart    IV. 


THE  TREATMENT  OF  GOUT  AND  OF 
GOUTY  CONDITIONS. 

CHAPTER  XIV. 

The  general  principles  on  inhich  the  treatment  of  gout  is 
based — Examination  of  the  urine  —  IVeatment  oj 
acute  gout — Diet  in  acute  gout — The  action  of 
colchicum — T'reatment  of  subacute  and  chronic  gout 
— Means  of  checking  the  excessive  formation  of  uric 
acid — Means  of  p7'omoiing  the  elimination  of  uric 
acid — Local  treatment  of  gouty  joints. 

THE    GENERAL    PRINCIPLES    ON   WHICH    THE   TREAT- 
MENT  OF   GOUT   IS   BASED. 

In  the  first  place  it  should  be  borne  in  mind 
that  no  routine  treatment  can  be  adopted  which  is 
suitable  to  all  cases.  The  nutritional  condition  of 
the  patient,  his  habits,  surroundings,  and  mode  of 
life,  constitute  factors  that  must  necessarily  modify 
the  treatment  of  individual  cases,  and  with  gout,  as 
with  so  many  other  diseases,  it  will  be  found  that 
each  individual  case  requires  separate  study,  and 
frequentl}^  special  treatment. 

The  treatment  of  gout  should  have  for  its  aim 
the  following  objects  :  (1)  the  treatment  of  the  gouty 
paroxysm  in  cases  of  acute  gout,  and  the  relief  of 
the  pain  as  speedily  as  possible ;  (2)  the  treatment 


200  The  Treatmrxt  of  Gout. 

I  of  the  subacute  or  chronic  condition  and  the  pre- 

(  vention  of  the  recuiTence  of  an  attack,  which  may 

\  be  effected  by  the  promotion  of  the  elimination  of 

I  uric  acid,  by  checking  any  excessive  formation  of 

I  uric  acid  that  occurs  in  some  subjects,  and  by  care- 

/  ful  attention  to  diet  and  general  hygiene :  and  (3) 

I  the  treatment  of  the  affected  joint  or  joints,  with 

1  the  object  of  removing  the   uratic  deposits,  and 

\  of  preventing  permanent  deformity. 

EXAMINATION   OF   THE   URINE. 

In  all  cases  of  gout  a  very  careful  examination 
of  the  urine  should  be  made,  and  it  is  especially 
important  to  endeavour  to  ascertain  whether  the 
kidney  affection  is  in  the  functional  or  organic 
stage.  The  indications  that  the  gouty  affection  of 
the  kidney  is  passing  from  the  functional  into  the 
organic  condition  are  the  existence  of  a  certain 
amount  of  polyuria,  a  low  specific  gravity  of  the 
urine — usually  from  1007  to  1016 — the  presence  of 
a  small  quantity  of  albumen,  which,  however,  may 
disappear  for  some  time  and  then  reappear,  the 
presence  of  a  few  granular  casts  if  a  careful  micro- 
scopical examination  is  made  after  centrifuging 
the  urine,  and  a  diminished  daily  excretion  of 
uric  acid  and  generally  of  urea.  It  is  most  impor- 
tant carefully  to  examine  the  urine  for  traces  of 
albumen,  and  for  the  presence  of  casts.  For  the 
latter  purpose  the  centrifugal  machine  should  be 
used,  as  the  casts,  when  present,  are  usually  present 
in  but  small  numbers,  and  are  otherwise  very  slow 
to  settle. 


Estimation  of  Uric  Acid.  20I 

It  is  desirable  before  commencing  treatment, 
and  from  time  to  time  during  treatment,  to  know 
the  amount  of  uric  acid  that  is  being  daily  ehmin- 
ated  in  proportion  to  the  body- weight  of  the 
patient.  This  determination  of  the  amount  of  uric 
acid  ehminated  must  be  made  on  a  sample  of  the 
mixed  urines  of  twenty-four  hours.  The  process 
that  I  always  employ  for  such  determinations  is  the 
Gowland- Hopkins  process  {see  p.  30),  which  is  a 
very  accurate  method  for  the  estimation  of  uric 
acid  in  urine.  The  mere  determination  of  the 
percentage  of  uric  acid  in  a  sample  of  the  urine 
is  useless,  as  it  constitutes  no  guide  to  the  actual 
amount  of  uric  acid  that  is  being  excreted.  It  is 
absolutely  necessary  to  determine  the  total  uric 
acid  elimination  for  the  twenty- four  hours,  and 
that  can  only  be  done  by  examining  a  sample  of 
the  mixed  urines  of  that  period.  Siniilarly  the 
determination  of  the  percentage  of  urea  in  a 
sample  of  the  urine  is  no  g^iide  to  the  amount 
of  nitrogenous  elimination  that  is  taking  place 
from  the  kidneys.  To  ascertain  that  factor  the 
total  output  of  urea  for  the  twenty-four  hours 
must  also  be  determined. 


THE  TREATMENT  OF  ACUTE  GOUT. 

For  the  treatment  of  the  gouty  paroxysm  the 
limb  should  be  placed  in  the  horizontal  position,  or 
slightly  elevated  above  the  level  of  the  body,  and  a 
cradle  arranged  so  as  to  take  the  weight  of  the  bed 
clothes  off  the  affected  part.  To  alleviate  the 
severe  pain  felt  in  the  affected  joint  warm  packs 


202  The  Treatment  of  Gout. 

should  be  arranged  round  it,  consisting  of  cotton- 
wool saturated  with  a  soothing  lotion,  and  then 
lightly  covered  with  oil-silk.  I  have  found  the 
following  lotion  most  useful  in  relieving  the  local 
pain : — 


Sodaa  carb. 
Linim,  belladoniife 

Tinct.  opii 

Aq.  ad      

-    5J- 

A  small  portion  of  the  lotion  should  be  mixed 
with  an  equal  quantity  of  hot  water,  and  then 
poured  on  cotton- wool  previously  arranged  round 
the  joint.  The  pack  should  be  changed  every 
eight  or  twelve  hours.  In  connection  with  the 
acute  paroxysm  no  attempt  at  local  depletion — 
such  as  the  application  of  leeches  to  the  inflamed 
joint,  blistering,  or  incisions  —  should  on  any 
account  be  made,  owing  to  the  great  liability  of 
thereby  extending  the  inflammatory  condition,  and 
so  producing  subsequent  ankylosis  or  deformity. 

For  the  internal  treatment  of  acute  gout  col- 
chicum  is  one  of  the  most  valuable  drugs  that  we 
possess.  It  should  be  especially  used  for  acute 
gout,  and  for  subacute  attacks  supervening  on 
chronic  gout.  If  used  continuously,  tolerance  is 
apt  to  be  acquired,  and  then  the  drug  ceases  to  act. 
At  the  commencement  a  large  dose  of  thirty  to 
forty  minims  of  colchicum  wine  should  be  given, 
followed  by  a  mixture  containing  in  each  dose  ten 
to  twenty  minims  of  the  wine  with  from  forty  to 
sixty  grains  of  citrate  of  potassium,  which  should 
be  administered  three  times  a  day.  The  citrate  of 
potassium,  which  is  given  for  its  combined  properties 


P  URGA  TI VES.  203 

of  acting^  as  a  diuretic  and  of  diminishinf'  the 
acidity  of  the  urine,  may,  if  desired,  be  given  as 
an  effervescing  mixture,  using  thirty  grains  of 
potassium  bicarbonate  to  twenty  grains  of  citric 
acid.  Colchicum  reduces  the  gouty  inflammation, 
reheves  the  pain,  and  shortens  the  attack.  It 
should  only  be  taken  under  medical  advice,  and 
should  never  be  given  in  such  doses  as  to  produce 
extreme  depression :  after  the  inflammation  of  an 
acute  attack  has  subsided  the  doses  of  colchicum 
should  be  gradually  diminished  until  it  is  left  off. 
Sir  Alfred  Garrod  regards  acute  gout  and  the  acut^ 
exacerbations  of  chronic  gout  as  the  chief  indica- 
tions for  employing  colchicum. 

From  three  to  four  grains  of  blue  pill  should  be 
given  the  first  night,  followed  by  a  dose  of  Epsom 
salts  in  the  morning.  Mercury  should  be  given 
only  in  sufficient  doses  to  produce  its  cholagogue 
effect,  as  owing  to  the  defective  action  of  the 
kidneys  the  mercury  absorbed  into  the  general 
system  may  be  eliminated  with  great  difficulty. 
In  my  opinion  it  is  advisable  in  the  treatment  of 
gouty  patients  in  the  acute  or  subacute  stages  to 
avoid  the  use  of  saline  purgatives  owing  their 
efficacy  to  salts  of  sodium,  on  account  of  the  un- 
doubted power  possessed  by  all  sodium  salts  of 
diminishing  the  solubility  of  sodium  biurate.  In 
the  employment  of  purgatives  for  gouty  patients 
the  great  object  is  not  to  produce  powerful 
purgation,  but  to  relieve  portal  congestion,  since 
a  congested  condition  of  the  liver  means  that  an 
excessive  quantity  of  glycocine  is  transmitted  to 


204  The  Treatment  of  Gout. 

the  kidneys,  where  an  excessive  quantity  of  uric 
acid  is  consequently  produced.  A  pill  containing 
either  two  grains  of  euonymin  or  a  quarter  of  a 
grain  of  podophyllin  combined  with  a  grain  of 
extract  of  h3^oscyamus  and  a  grain  and  a  half  of 
the  compound  extract  of  colocynth  will,  in  many 
eases,  be  found  to  be  very  useful. 

If  the  pain  of  an  acute  attack  of  gout  is  so 
severe  as  to  prevent  sleep,  chloral,  sulphonal,  or 
trional  may  be  given,  or  a  full  dose  of  extract  of 
hyoscyamus  given  with  blue  pill  at  night  will,  in 
some  cases,  act  as  a  very  useful  anodj^ne.  The 
administration  of  opium  or  morphine  should,  if 
possible,  be  avoided  owing  to  the  risk  of  its  deficient 
elimination  on  account  of  the  kidney  affection,  and 
also  on  account  of  its  diminishing  the  amount  o^ 
urine,  and  its  tendency  to  derange  digestion  and  to 
check  hepatic  metabolism. 

DIET   IN    ACUTE   GOUT. 

During  an  attack  of  acute  gout  a  diet  must  be 
given  which,  in  the  first  place,  shall  be  non- 
irritating  to  the  aftected  kidneys,  and,  in  the  second 
place,  shall  be  one  that  does  not  produce  an  ex- 
cessive quantity  of  uric  acid.  For  the  first  day  or 
two  of  an  acute  attack  the  patient  should  be 
restricted  to  a  milk  diet,  which  may  consist  of 
milk,  arrowroot  and  milk,  bread  and  milk,  milk 
puddings  made  with  rice,  sago,  or  tapioca,  and  tea 
made  with  boiling  milk  instead  of  with  water. 
Weak  tea  with  cold  toast  thinly  buttered  may  also 
be  taken.     The  free  drinking  of  hot  or  cold  water, 


The  Action  of  Colchicum.  205 

of  salutaris  water,  or  of  some  mineral  water  free  from 
sodium  salts  (for  list  of  such  waters,  nee,  p.  280), 
should  be  encouraged.  The  milk  diet  should  bo 
continued  until  the  acute  inflammation  is  sub- 
siding, which  stage  is  indicated  by  the  lessening  of 
the  pain,  and  by  the  pitting  on  pressure  of  the 
affected  parts.  No  alcohol  in  any  form  should  be 
given  during  this  stage,  unless  there  are  strong 
reasons  for  its  administration,  such  as  a  weak  action 
of  the  heart  and  a  feeble,  irregular  pulse,  when  a 
little  well-matured  whisky  diluted  with  salutaris 
water  will  prove  the  best  form  of  alcohol  Beef  tea 
and  any  of  the  meat  extracts  or  essences  should  be 
avoided  at  all  times  by  gouty  patients  owing  to  the 
tendency  they  have  to  irritate  the  kidneys,  and  so 
to  interfere  with  the  elimination  of  uric  acid.  With 
the  subsidence  of  the  acute  attack  the  patient  may 
return  to  a  more  liberal  diet,  but  care  should  be 
taken  to  avoid  anything  indigestible.  For  the 
dietary  suitable  for  gouty  subjects  after  the  acute 
attack  has  subsided,  see  pp.  222 — 225. 

THE   ACTION   OF   COLCHICUM. 

Although  no  satisfactory  explanation  of  the 
beneficial  action  of  colchicum  in  gout  has  hitherto^ 
been  put  forward,  I  believe  that  its  beneficial  effect 
is  mainly  dueto  its  diminishing  the  uric  acidpro;^ 
ductiqn^  thereby  arresting  the  absorption  of  uric 
acid  from  the  kidneys,  and  so  preventing  the 
further  deposition  of  biurate  in  the  affected  parts. 
Colchicum  is  a  powerful  direct  cholagogue,  and  it 
is  probably  owing  to  its  action  on  the  liver  that  its 


2o6  The  Treatment  of  Gout. 

efficacy  in  mitigating  the  severity  of  the  pain  and 
relieving  an  attack  of  gout  is  due.  If,  as  a  chola- 
gogue,  it  inhibits  the  formation  of  glycocine,  then 
the  amount  of  uric  acid  formed  in  the  kidneys 
must  be  diminished,  and  if  the  uric  acid  formation 
is  lowered  to  the  quantity  that  can  be  eliminated 
by  the  affected  kidneys,  then  the  absorption  of 
quadriurates  from  the  kidneys  into  the  general 
circulation  is  prevented,  and  so  the  formation  of 
further  gouty  deposits  is  arrested.  This  view 
renders  intelligible  the  efficacy  of  colchicum  not 
only  in  connection  with  articular  gout,  but  also  in 
connection  with  the  various  forms  of  irregular  gout. 
The  explanation  just  given  of  the  mode  of 
action  of  colchicum  is  at  once  supported  by  the 
fact  recorded  by  so  many  observers  that  the  uric 
acid  elimination  is  always  diminished  during  the 
period  of  administration  of  colchicum,  whereas  the 
elimination  of  urea  is  practically  unaffected  by 
the  drug.  The  following  table  (Table  LYIL)  shows 
the  diuiinished  elimination,  and,  as  I  believe,  the 
diminished  formation  of  uric  acid,  that  occurred 
during  the  administration  of  colchicum  to  one  of 
my  patients  while  suffering  from  an  attack  of  sub- 
acute gout  of  both  hands  and  knees.  That  deficient 
production  of  uric  acid  accompanied  the  deficient 
excretion  was  shown  by  the  fact  that  the  gouty 
affection  of  the  joints  rapidly  improved  during  the 
treatment  with  colchicum,  whereas  if  the  formation 
of  uric  acid  had  remained  the  same,  and  merely 
deficient  elimination  of  it  had  occurred,  the  articular 
condition  would  have  become  worse. 


The  Action  of  Colchicum.  207 


TABLE    LVII. 

Shotcing  the  decreased  elimination  of  uric  acid  in  a  case  of  sub-acute 
gout  during  the  administration  of  colchicum. 


Urir  acid  in 
graiinnes. 


Daily   elimination  at   the  commencement  of  the 
attack 


0-438 


Average  of   the   daily  eliminat'ons  for  fourteen 
days   "while   under   treatment  with  colchicum. 
(Vin.    colchici    iiixxx  were  given   as   the  fh'st 
dose,  and  then  -»!_  xv  three  times  a  day  through-     | 
out  the  fourteen  days  of  treatment.)     ...         ...     '         0-234 


This  diminished  excretion  of  uric  acid  that 
occurs  during  the  administration  of  colchicum  is 
a  good  sign,  since  it  points,  in  my  opinion,  to 
diminished  formation  of  uric  acid.  It  is  in  marked 
contrast  to  the  action  of  sodium  salicylate,  which 
considerably  increases  the  excretion  of  uric  acid 
by  increasing  its  formation  in  the  kidneys.  As 
previously  stated  {see  pp.  196, 197),  the  employment 
of  salicylates  in  the  treatment  of  gout  is,  in  my 
opinion,  contra-indicated. 

Although  colchicum  does  not  directly  affect  the 
solution  of  uratic  deposits,  yet  indirectly  it  may 
produce  that  result,  since,  by  diminishing  the 
formation  of  uric  acid,  it  allows  the  kidneys  to 
eliminate  the  sodium  quadriurate  circulating  in 
the  blood  of  the  gouty  patient,  and  if  the  blood  can 
be  kept  free  from  quadriurate,  then  the  solution  of 
the  sodium  biurate  from  the  joints  and  tissues, 
where  it  is  deposited,  will  slowly  but  surely  proceed. 
The   mitigation   of  the   pain   of    an   acute   gouty 


2o8  The  Treatment  of  Gout. 

paroxysm  is  probably  owing  to  colchicum  acting  as 
a  cardio-vascular  depressant,  lowering  the  tension 
and  frequency  of  the  pulse,  and  so  relieving  the 
pressure  and  pain  felt  in  the  affected  joint, 

THE  TREATMENT  OF  SUBACUTE  AND  CHRONIC  GOUT 

Means  of  checking  the  excessive  formation  of 
uric  acid. — These  consist  in  careful  attention  to 
diet  and  regimen,  the  promotion  of  the  metabolism 
of  the  liver,  so  as  to  check  the  excessive  production 
of  the  antecedents  of  uric  acid,  and  in  the  relief  of 
congestion  of  the  portal  system,  which  can  be 
effected  by  keeping  the  bowels  open  at  least  once 
a  day.  In  addition  to  colchicum,  which  may  be 
given  in  small  doses,  guaiacum  may  very  usefully 
be  administered  as  an  alterative  which  stimulates 
the  metabolism  of  the  liver,  and  also  affords  relief 
to  the  portal  system.  From  five  to  ten  grains 
of  guaiacum  resin  should  be  given  in  cachets 
two  or  three  times  a  day,  according  to  the  effect 
on  the  bowels,  since  guaiacum  generally  acts  as  a 
laxative.  If  constipation  occur,  a  sulphur  and 
guaiacum  tablet,  or  a  dose  of  compound  liquorice 
powder,  should  be  taken  at  night.  An  occa- 
sional dose  of  bkie  pill  and  euonymin,  followed 
by  a  purge  of  Epsom  salts,  will  be  iound  useful. 
Sir  Alfred  Garrod  considers  that  guaiacum  relieves 
gouty  inflammation,  and  that  a  similar  result  is 
produced  by  the  administration  of  serpentary.  If 
guaiacum  is  given  in  too  large  doses  it  may  produce 
a  papular  or  urticarial  rash  accompanied  by  con- 
siderable itching.     If  the  patient  is  suffering  from 


Elimination  of  Uric  Acid.  209 

atony  and  debility  of  the  stomach,  mix  vomica  or 
strychnine  may  be  given  with  potassium  citrate. 
Iron  preparations  are  not  as  a  rule  well  tolerated  by 
the  gouty,  but  if  ancemia  is  present  the  citrate  of 
iron  and  ammonium  or  the  carbonate  of  iron  Avill  be 
found  the  best  to  administer. 

Means  of  promoting  the  elhnination  of  uric 
acid. — The  elimination  of  uric  acid  may  be  eftected 
by  medicinal  treatment,  and  by  diet  and  regimen. 
Citrate  of  potassium  should  be  employed  as  a 
diuretic  which  increases  the  volume  of  the  urine, 
and  at  the  same  time  diminishes  its  acidity.  The 
use  of  the  citrate  of  potassium  ma}^  with  advantage 
be  pushed  until  moderate  alkalinity  of  the  urine  is 
produced,  as  by  such  means  the  quadriurates  are 
rendered  more  soluble  and  more  stable  than  they 
are  in  acid  urine,  and  so  the  tendency  to  the 
deposition  of  uric  acid  or  sodium  biurate  in  the 
kidney  tissues  is  removed.  Free  diuresis  should 
also  be  encouraged  by  the  drinking  of  sufficient 
quantities  of  water.  A  patient  suffering  from 
gout  should  avoid,  as  far  as  possible,  the  use  of 
common  salt  at  table,  owing  to  the  power  it  pos- 
sesses of  diminishing  the  solubility  of  sodium 
biurate,  and  thereby  hastening  the  precipitation  of 
that  body.  The  dietetic  treatment  of  chronic  gout 
is  described  on  pp.  222 — 225. 

Further  treatment  of  chronic  gout. — The  en- 
largement and  tenderness  of  the  gouty  joints  is  due 
to  two  causes — the  deposition  of  sodium  biurate 
in  the  cartilaofes  and  fibrous  structures,  and  a 
chranic  inflammatory  thickening  of  the  fibrous 
o 


2IO  The  Treatment  of  Gout. 

tissues.  For  the  reduction  of  this  last-mentioned 
thickening,  as  well  as  for  painful  gout  of  the  sole  of 
the  foot,  and  for  gouty  neuralgic  affections,  iodide 
of  potassium  given  internally  is  a  useful  remedy. 
This  drug  should  not,  however,  be  regarded  as  a 
solvent  of  gouty  deposits,  and  it  is  contra-indicated 
if  advanced  kidney  disease  exists.  It  should  be 
given  in  doses  of  five  to  ten  grains  three  times  a 
day,  and  may  usefully  be  combined  with  from  five 
to  ten  minims  of  tincture  of  iodine.  Sir  Alfred 
Garrod  advises  the  administration  of  guaiacum  in 
those  cases  where  the  gouty  pains  are  relieved  by 
the  application  of  warmth,  but  considers  that  it 
is  contra-indicated  when  any  marked  inflammatory 
symptoms  are  present,  as  shown  by  the  increase  of 
pain  when  the  patient  is  warm  in  bed.  In  such 
cases  potassium  iodide  is  likely  to  be  more  bene- 
ficial than  guaiacum.  The  lithium  salts  are  not, 
in  my  opinion,  solvents  of  gouty  deposits  {see  pp. 
183, 184, 189),  but  since  they  are  powerful  diuretics 
they  may,  on  that  account,  be  of  some  use  in  the 
treatment  of  chronic  gout.  They  should  never, 
however,  be  given  in  sufficient  quantities  to  keep 
the  urine  alkaline,  as  their  depressing  effect  in  such 
doses  is  too  great. 

If  the  signs  of  organic  renal  mischief  exist 
{see  p.  200),  then  particular  attention  must  be  paid 
to  the  prevention  of  an  excessive  formation  of  uric 
acid.  This  can  be  accomplished  by  placing  the 
patient  on  a  suitable  diet,  by  promoting  elimination 
from  the  kidneys  by  the  administration  of  suitable 
diuretics,  such  as  potassium  citrate  and  ammonium 


Treatment  of  Jo/xts.  2 1 1 

acetate,  and  by  the  thorough  flushing  of  the 
kidneys  by  a  water  as  free  as  possible  from  sodium 
salts.  If  marked  albuminuria  occurs  then,  in 
addition  to  the  above-mentioned  treatment,  vapour 
baths  or  Turkish  baths  may  be  employed,  provided 
they  do  not  produce  debility. 

THE    LOCAL    TllEATMEXT   OF   GOUTY   JOINTS. 

If  much  swelling  of  a  joint  persists,  the  limb 
should  be  elevated  as  much  as  possible,  and  a  light 
flannel  bandage  applied  to  the  joint.  If  the  oedema 
persists,  the  hot  douche  followed  by  sponging  with 
a  cold  strono-  solution  of  common  salt  will  be  found 
serviceable.  The  application  of  the  so-called 
solvents  of  uric  acid  externally  to  affect  3d  joints  is 
useless,  as  they  are  not  solvents  of  sodium  biurate. 
Careful  massage  and  gentle  exercise  of  the  stiftened 
joints  should  be  employed,  but  only  when  con- 
valescence is  fairly  established :  massage  and 
muscular  movement  increase  the  flow  of  lymph  in 
the  lymph  channels,  and  so  tend  to  promote  the 
removal  of  uratic  deposits,  and  to  increase  general 
metabolism.  For  the  stiflhess  and  thickening  of 
joints,  careful  rubbing  with  iodide  of  potassium  and 
soap  liniment  or  with  the  compound  camphor 
liniment  may  be  resorted  to. 

The  thermal  baths  of  Bath,  Buxton,  Aix-les- 
Bains,  and  other  spas,  and  mud  baths,  are  useful  in 
the  treatment  of  cases  of  chronic  articular  gout. 
Treatment  by  means  of  baths  should,  however,  be 
avoided  by  patients  suffering  from  acute  gout,  by 
elderly  patients,  and  by  those  suffering  from  any 


212  The  Treatment  of  Gout. 

serious  cardiac  affection.  Successful  results  have 
been  reported  from  the  localised  application  of  very 
hot  dry  air,  which  appears  not  only  to  relieve  the 
pain  and  congestion  of  the  joints,  but  also  to  assist 
in  the  dispersion  of  the  gouty  deposit,  probably  by 
increasing  the  circulation  in  the  various  structures 
of  the  affected  joint.  After  convalescence  as  much 
exercise  as  possible,  short  of  fatigue  and  discomfort, 
should  be  taken  in  the  open  air.  Cycling  is  an 
excellent  exercise  for  the  gouty,  since  it  furnishes 
good  muscular  movement  in  the  open  air  withovit 
the  gouty  joints  having  to  bear  the  weight  of 
the  body. 


CHAPTER   XV. 

Treatment  of  retrocedent  or  itietastatic  gout — Treatment 
of  tlie  various  forms  of  irregular  gout — Treatramd 
of  gouty  glycosuria  and  diabetes — Preventive  treat- 
ment of  gout — Diet  in  gout — Alcohol  in  gout. 

THE  TREATMENT  OF  RETROCEDENT  OR  METASTATIC 

GOUT. 

Immediate  treatment.  —  If  tlie  symptoms  are 
urgent  some  brandy  should  be  immediately  given, 
and,  if  necessary,  a  hypodermic  injection  of  mor- 
phine should  be  administered,  provided  marked 
albuminuria  does  not  exist  If  the  metastatic 
seizure  is  a  severe  one,  and  especially  if  it  affects 
either  the  heart  or  brain,  it  may  be  desirable  to 
reinduce  an  attack  of  articular  gout  by  placing  the 
leet  in  a  hot  mustard-and-water  bath,  containing  a 
full  tablespoonful  of  flour  of  mustard  to  a  gallon 
of  water. 

Treatment  of  the  gastro-intestinal  form. — A 
mustard  leaf  should  be  applied  to  the  epigastrium, 
and  a  mixture  containing  bismuth  subcarbonate, 
sodium  bicarbonate,  and  hydrocyanic  acid  should 
be  given.  If  there  is  much  depression  suitable 
stimulants  must  be  employed. 

Treatment  of  the  ca/rdiac  form. — Heart  tonics, 
such  as  digitalis,  convaUaria,  or  strophanthus,  and 


214  The  Treatment  of  Gout. 

brandy,  should  be  administered.  A  mustard  leaf 
may  be  applied  to  the  epigastrium.  If  an  anginal 
attack  occurs,  then,  in  addition  to  this  treatment,  a 
dose  of  nitroglycerine  should  be  given  at  once,  or 
an  inhalation  of  nitrite  of  amyl  employed,  and,  if 
necessary,  a  mustard  leaf  should  be  placed  over  the 
prtecordial  region.  For  the  treatment  of  syncopal 
attacks  the  patient  should  be  immediately  placed 
in  the  recumbent  position,  with  the  foot  of  the  sofa 
or  bed  raised ;  some  hot  brandy  and  water  should 
be  given,  warmth  and  friction  applied  to  the 
extremities,  and  a  mustard  leaf  placed  over  the 
epigastrium. 

Treahneiit  of  the  cerebral  form. — If  the  patient 
is  plethoric,  and  if  the  pulse  is  hard,  and  stupor  or 
coma  supervene,  venesection  should  be  performed, 
and  from  eight  to  sixteen  ounces  of  blood  with- 
drawn ;  in  less  urgent  cases  six  leeches  may  be 
applied  to  the  mastoid  region.  Five  grains  of 
calomel  should  afterwards  be  administered  by  the 
mouth,  and  a  turpentine  enema  given. 

THE   TREATMENT   OF   THE  VARIOUS   FORMS   OF 
IRREGULAR  GOUT. 

Affections  of  the  gastro-intestinal  tract  and  of 
the  air-passages  and  lungs  due  to  irregular  gout 
require  treatment  on  general  principles.  For  lists 
of  the  mineral  waters  best  suited  for  these  forms 
of  irregular  gout,  see  p.  241. 

GoiUy  vertigo  is  generally  due  to  gastric  dis- 
turbance, which  then  requires  suitable  treatment. 
If  the  vertigo  is  of  central  origin,  then  the  ordinary 


The  Gouty  Heart.  215 

medicinal   treatment   for   acute    gout    should    be 
employed. 

The  (jovdy  heart  is  associated  with  fatty  de- 
generation of  the  cardiac  walls,  and  is  mainly  met 
with  among  sufferers  from  irregular  gout.  The 
condition  is  generally  evidenced  by  prsecordial 
pain  or  oppression,  vertigo,  faintness,  palpitation, 
or  irregular  cardiac  action,  insomnia,  and  slight 
anginal  attacks;  towards  the  end  of  an  attack 
a  cold  sweat  generally  breaks  out  on  the  surface 
of  the  body,  and  is  followed  by  flatulent  eructa- 
tions, after  which  the  attack  subsides.  The  treat- 
ment should  be  rest  in  the  recumbent  position, 
and  a  small  dose  of  blue  pill  or  calomel,  followed 
by  a  purge  of  Epsom  salts,  should  be  administered. 
If  the  pulse  is  of  low  tension  a  mixture  containing 
convallaria  and  strychnine  will  be  suitable.  If 
anginal  attacks  occur,  nitroglycerine  or  erythrol 
tetra-nitrate  may  be  given  by  the  mouth,  or  in- 
halations of  nitrite  of  amyl  employed.  Iodide  of 
potassium  is  also  a  very  useful  drug  when  there 
is  much  pain.  The  patient  must  be  carefully 
dieted  {see  pp.  222 — 225),  and  graduated  exercise, 
at  first  of  a  passive  nature,  such  as  the  Schott 
treatment,  and  later  of  an  active  nature,  may  be 
very  beneficial.  The  action  of  the  bowels  should 
be  properly  regulated,  and  entire  abstention  from 
tobacco  smoking,  or  extreme  moderation  m  its 
use,  should  be  advised. 

Angina  pectoris. — In  anginal  attacks  in  gouty 
subjects  the  pulse  is  generally  one  of  high  tension 
without  the  existence  of  any  necessary  association 


2i6  The  Treatment  of  Gout. 

of  atheroma  of  the  vessels.  For  the  immediate 
rehef  of  the  actual  attacks  nitrogl3'cerine  is  the 
best  drug  to  employ,  although  in  rare  cases  nitrite 
ol  amyl  may  be  found  more  efficacious.  Stimulants 
and  morphine  administered  hypodermically  should 
also  be  employed  if  necessary.  For  some  days 
after  an  attack  nitroglj^cerine  in  doses  of  one- 
hundredth  of  a  grain  should  be  given  two  or  three 
times  a  day.  If  organic  cardiac  mischief  exist,  the 
condition  must  be  suitably  treated  on  general  prin- 
■ciples.  In  cases  of  anginal  attacks  occurring  in 
gouty  subjects,  as  soon  as  the  severe  pain  has  been 
relieved  by  the  administration  of  nitroglj'cerine,  a 
pill  containing  one  grain  of  the  acetic  extract  of 
colchicum  and  three  grains  of  blue  pill  should  be 
given  at  night  and  should  be  ibllowed  by  a  dose  of 
Epsom  salts  in  the  morning.  When  the  adminis- 
tration of  nitroglycerine  is  discontinued  citrate  of 
potassium  and  iodide  of  potassium  should  be  given 
for  some  time  three  times  a  day. 

Pseudo- angina  pectoris. — For  the  treatment  of 
this  affection  a  dose  of  hot  brandy  and  water  should 
be  given  at  once,  and  a  mustard  leaf  should  be 
applied  to  the  epigastrium.  On  the  subsidence  of 
the  severe  symptoms  a  pill  containing  one  grain  of 
the  acetic  extract  of  colchicum  and  three  grains  of 
blue  pill  should  be  given  at  night,  and  should  be 
followed  by  a  dose  of  Epsom  salts  in  the  morning. 

Gouty  jy] debit  is. — For  the  treatment  of  this 
fairly  common  form  of  irregular  gout  the  patient 
should  be  kept  in  the  recumbent  position,  and  any 
sudden  movement  of  the  affected  limb  must  be 


Sciatica  axd  Neuritis.  217 

prevented,  on  account  of  the  danger  of  detaching  a 
portion  of  thrombus  and  the  occurrence  of  conse- 
quent embolism  of  the  pulmonary  artery.  Equal 
parts  of  glycerine  and  extract  of  belladonna  should 
be  smeared  over  the  affected  part,  and  a  linseed 
poultice  with  some  of  the  glycerine  and  extract  of 
belladonna  spread  on  the  surface  should  be  applied 
and  renewed  every  six  hours.  In  addition  to  this 
the  ordinary  treatment  of  the  gouty  state  must  be 
resorted  to. 

Gouty  sciatica. — For  the  treatment  of  this 
painful  affection  the  patient  must  be  kept  in  the 
recumbent  position,  and  in  severe  cases  the  pain 
should  be  relieved  by  a  hypodermic  injection  of 
morphine.  Ammonium  chloride,  given  in  doses 
of  thirty  to  forty  grains  three  times  a  day,  is  a 
very  useful  drug  in  the  treatment  of  this  form  of 
irregular  gout.  Two  grains  of  salicylate  of  quinine 
should  also  be  given  in  a  pill  two  or  three  times  a 
day.  In  cases  of  gouty  sciatica  the  ordinary  treat- 
ment of  the  gouty  state  must  be  resorted  to. 

Gouty  neuritis. — Blistering  along  the  course  of 
the  affected  nerve-trunk  is  the  most  rapid  way  of 
relieving  this  painful  affection.  If  such  a  mode 
of  treatment  should  not  be  considered  desirable, 
then  iodine  liniment  may  be  painted  along  the 
-course  of  the  nerve-trunk,  and  hot  linseed  poultices 
applied  as  soon  as  the  iodine  is  dry,  and  kept  in 
position  by  a  bandage  loosely  applied.  Internally, 
iodide  of  potassium  and  iodine  (for  the  doses  see 
.p.  210)  combined  with  small  doses  of  perchloride 
of  mercury  should  be  given. 


2i8  The  Treatment  of  Gout. 

Diseases  of  the  skin  associated  with  gout. — In 
dealing  with  any  gouty  skin  affection  the  ordinary 
treatment  of  the  skin  disease  should  be  combined 
with  the  general  treatment  of  the  underlying 
gouty  condition,  and  careful  attention  should 
especially  be  paid  to  the  diet.  Many  of  the  gouty 
skin  affections  are  considerably  benefited  by  a 
course  of  waters  and  baths  at  certain  spas  (a  list 
of  these  spas  is  given  on  pp.  239,  240).  The  severe 
itching  attending  pruritus  and  urticaria  is  gener- 
ally relieved  by  the  application  of  the  following 
lotion : — 

Liq.  plumbi  subacet.      ...         ...     5i] 

Tinct.  opii  ...         ...         ...     5iv 

Aq.  rosaj  ad        ...         ...         ...     ^viij 

Rubbing  the  skin  with  a  menthol  cone 
moistened  with  water  is  frequently  useful  in 
relieving  the  irritation.  For  the  treatment  of  dry 
skin  eruptions  Sir  William  Roberts  recommends 
the  skin  to  be  rubbed  with  a  piece  of  smooth  hard 
paraffin  night  and  morning,  so  as  to  leave  a  delicate 
coating  on  the  skin,  which  then  probably  acts  by 
protecting  the  cutaneous  surface  from  the  air. 

Renal  calculi. — For  the  treatment  of  uric  acid 
renal  calculi  citrate  of  potassium  should  be  given  in 
full  doses,  so  as  to  produce  a  moderate  alkalinity  of 
the  urine.  By  this  means  the  further  deposition  of 
free  uric  acid  in  the  kidneys  is  prevented,  and  the 
alkaline  urine,  moreover,  gradually  carries  into 
solution  the  uric  acid  already  deposited.  The  free 
drinking  of  ordinary  water  or  of  one  of  the  mineral 
waters  of  the  simple  kind  (see  p.  230)  should  be 
advised. 


Glycosuria  and  Diabetes.  219 

Irritable  teiwper. — For  the  treatment  of  the 
irritable  temper  of  gout,  Dr.  Lauder  Brunton 
recommends  the  administration  of  twenty  grains 
of  bicarbonate  of  potassium  and  ten  to  twenty 
grains  of  bromide  of  potassium. 

THE     TREATMENT     OF     GOUTY     GLYCOSURIA     AND 
GOUTY    DIABETES. 

Dietetic  treatment. — Careful  dietetic  treatment 
should  be  resorted  to  without,  however,  restricting 
the  diet  too  much.  An  excessively  nitrogenous 
diet  is  to  be  avoided  as  tending  to  accentuate  the 
gouty  condition,  but  no  hard  and  fast  rules  as  to 
the  amount  of  diet  can  be  laid  down.  Each  case 
must  be  treated  by  ascertaining  what  amount  of 
proteids,  fats,  and  carbohydrates  is  best  borne  by 
the  individual.  Toasted  bread,  milk,  and  milk 
puddings  made  with  rice,  sago,  and  tapioca  are 
generally  permissible  in  this  form  of  glycosuria. 
The  best  test  of  the  suitability  of  the  diet  is  the 
fact  that  the  weight  of  the  patient  is  not  diminish- 
ing, Avhile,  at  the  same  time,  the  excretion  of  sugar 
is  becoming  less.  The  patient  should,  therefore,  be 
weighed  once  a  w^eek,  and  the  whole  of  the  urine 
for  twenty-four  hours  should  be  collected  once  a 
w^eek,  measured,  and  the  quantity  of  sugar  deter- 
mined in  a  sample  of  the  mixed  urines,  so  that  the 
total  output  of  sugar  for  the  twenty-four  hours 
may  be  known. 

Medicinal  treatment. — A  pill  containing  one 
grain  of  blue  pill,  one  grain  of  acetic  extract  of 
colchicum,  and  tAvo  grains  of  euonymin  should  be 


220  The  Treatment  of  Gout. 

given  every  other  night.  A  mixture  containing 
thirty  grains  of  ammonium  chloride  and  fifteen 
minims  of  dikite  nitro-hydrochloric  acid  in  each 
dose  should  be  taken  three  times  a  day ;  this 
mixture  acts  as  a  stimulant  to  hepatic  metabolism. 
Opium  and  its  alkaloids  are  best  avoided.  For 
a  list  of  the  mineral  waters  best  suited  for  the 
treatment  of  gouty  glycosuria  and  gouty  diabetes, 
see  p.  241. 

THE  PREVENTIVE  TREATMENT  OF  GOUT. 

If  uric  acid  is  manufactured  in  the  kidneys  and, 
in  gout,  is  absorbed  therefrom  into  the  general 
circulation  only  when  the  kidneys  are  incapable 
of  o^ettinQf  rid  of  the  whole  of  the  uric  acid,  then 
whatever  will  promote  the  elimination  of  the  uric 
acid,  and  thereby  prevent  its  absorption  into  the 
general  circulation,  will  strike  at  the  origin  of  the 
development  of  gout.  This  can  be  effected  by  (1) 
the  promotion  of  increased  diuresis,  by  which 
means  the  solution  and  removal  of  the  quadriurates 
from  the  kidneys  is  encouraged ;  (2)  by  the  produc- 
tion, at  all  events  intermittently,  of  a  moderate 
degree  of  alkalinity  of  the  urine,  by  which  means 
the  quadriurates  are  rendered  more  soluble  and 
more  stable  than  they  are  in  an  acid  urine,  and  so 
the  tendency  to  the  deposition  of  uric  acid  or  of 
sodium  biurate  in  the  kidney  tissues  is  removed  ; 
and  (3)  by  stimulation  of  the  metabolism  of  the 
liver  and -of  the  kidney  cells  engaged  in  the  ex- 
cretion of  uric  acid.  The  preventive  treatment  of 
gout  consists  in  the  adoption  of  measures  which 


Preventive  Tkeatmest.  221 

have   for   their   aim   the   carry mg    out    of    these 
various  points. 

The  first  effect  can  be  secured  by  the  patient 
drinking  a  sufficient  quantity  of  ordinary  water,  or 
of  a  suitable  mineral  water.  The  second  effect 
is  attained  by  the  consumption  of  sufficient  quan- 
tities of  vegetable  food,  and  by  the  occasional 
administration  of  citrate  of  potassium.  The  third 
effect  is  secured  by  the  administration  of  guaiacum 
and  other  suitable  cholagogues,  such  as  an  occa- 
sional pill  containing  two  grains  of  blue  pill  and 
two  gi'ains  of  euonymin  given  at  night,  and  followed 
by  a  dose  of  Epsom  salts  in  the  morning.  Sir 
Alfred  Garrod  considers  that  guaiacum  taken  in 
the  intervals  of  attacks  of  gout  is  a  powerful 
prophylactic,  that  it  does  not  appear  to  lose  its 
prophylactic  power  by  long-continued  use,  and 
that  only  in  the  cases  of  a  few  persons  does  the 
drug  disagree.  I  have  employed  guaiacum  for 
some  time  as  a  prophylactic  in  gout,  and  can 
entirely  corroborate  Sir  Alfred  Garrod's  opinion  as 
to  its  great  utihty  under  such  conditions. 

To  prevent,  as  far  as  possible,  the  recurrence 
of  gout  the  patient  should  also  give  careful 
attention  to  diet  on  the  lines  laid  down  in 
pp.  222—225.  Regular  habits  of  life,  with 
regular  and  sufficient  exercise,  should  be  encour- 
aged, and  constipation  should  be  zealously  avoided. 

Briefly  stated,  the  individual  who  is  subject 
to  gout,  and  who  wishes  to  prevent  a  recurrence 
of  the  disease,  should  lead  an  active  and  an  ab- 
stemious life. 


222  The  Treatment  of  Gout 

diet  in  gout. 

A  rational  mixed  diet  is  the  one  best  suited  for 
gouty  patients,  care  being  taken  to  avoid  excess. 
The   assumption   that   a   purely  vegetable  diet  is 
best  for  the  gouty  is  erroneous,  since  the  production 
of  uric  acid  depends  on  the  ingestion  of  proteid 
matter,  and   it   makes   no  difference  whether  the 
proteid  matter  be  of  animal  or  vegetable   origin. 
At  the  same  time  it  must  be  borne  in  mind  that 
since  animal  food  is  so  much  richer  in   proteids 
than  a  vegetable  diet,  the  amount  of  the  former 
taken   by   the   gouty   should   be   strictly   limited. 
Moreover,  the  results  of  the  series  of  investigations 
summarised  on  pp.  172 — 175  show  that,  whereas  the 
mineral  constituents  of  meat  exercise   a   marked 
effect    in   diminishing   the   solubility   of  a   gouty 
deposit,   the   mineral   constituents  of  most   vege- 
tables exercise  a  marked  power  in  increasing  its 
solubility.    The  vegetables  the  mineral  constituents 
of  which  I  find  are  most  efficacious  in  this  respect 
are   spinach,   Brussels   sprouts,   potatoes,   cabbage, 
and  French  beans.     At  the  same  time  it  must  be 
borne   in  mind    that  with   certain   patients  some 
of  these  vegetables   may   tend   to   produce   some 
form   of    dyspepsia,   and    I    cannot   too    strongly 
urge   that   in   the   dieting  of  the  gouty  no  hard 
and  fast  rules  can  be  laid  down,  but  the  idiosyn- 
crasy of  each  patient  to  various   articles   of  diet 
must  be  made  the  subject  of  careful  observation 
and  study.    Due  consideration  should  also  be  given 
to  the  patient's  experience  of  what  articles  of  diet 


Diet  in  Gout.  223 

disagree  and  agree  with  him.  If,  during  the  treat- 
ment of  gout,  an  attack  of  gouty  dyspepsia  should 
at  any  time  intervene,  then  a  milk  diet  should  be 
employed  until  the  dj-speptic  symptoms  have  abated. 
It  is  most  important  that  the  gouty  patient  should 
take  a  sufficiency  of  water  to  drink,  so  that  the 
various  organs  are  well  flushed,  the  removal  of  the 
gouty  deposits  encouraged,  and  the  specific  gravity 
of  the  urine  kept  moderately  low.  The  quantity 
of  fluids  taken  in  the  twenty-four  hours  should  not 
be  less  than  three  and  a  half  pints,  and  may  even 
with  advantage  reach  to  four  and  a  half  pints. 

The  following  plan  gives  an  indication  of  the 
diet  to  be  recommended  to  gouty  subjects  : — - 

Morning. — Half  a  pint  to  a  pint  of  hot  water 
flavoured  with  a  slice  of  lemon  peel  should  be 
slowly  sipped  immediately  on  rising. 

Breakfast. — A  selection  may  be  made  from  the 
following  articles  of  diet,  according  to  the  taste 
of  the  patient : — Porridge  and  milk,  whiting,  sole 
or  plaice,  fat  bacon,  eggs  cooked  in  various  Avays, 
dry  toast  thinly  buttered,  and  tea  infused  for 
three  minutes  and  then  strained  from  the  leaves. 

Lunch  and  dinner. — No  soup  should  be  taken 
at  either  msal.  The  varieties  of  fish  most  suitable 
to  the  gouty  are  whiting,  sole,  turbot,  and  plaice. 
Meat  should  be  taken  at  only  one  meal,  and  then  in 
moderate  quantity.  Beef,  mutton,  chicken,  turkey, 
pheasant,  and  calf's  sweetbread  are  admissible. 
Salted  meat,  salted  and  smoked  fish,  and  shell  fish, 
with  the  exception  of  oysters,  are  best  avoided. 
All  articles  of  food  pickled  in  vinegar  should  also 


224  The  Treatment  of  Gout. 

be  avoided.  Two  vegetables  should  be  taken  at 
both  lunch  and  dinner,  and  in  abundant  quantities. 
The  vegetables  that,  in  my  opinion,  should  be 
avoided  by  the  gouty  are  asparagus,  tomatoes,  and 
green  peas.  Asparagus  is  apt  to  prove  irritating  to 
the  kidneys  of  gouty  subjects,  and  also  is  liable  to 
produce  a  temporary  glycosuria,  probably  from 
some  irritant  effect  on  the  liver.  Anj^  of  the  other 
ordinary  vegetables  may  be  taken,  but  those  that  I 
consider  most  likely  to  prove  beneficial  to  gouty 
subjects  are,  as,  indeed,  has  already  been  mentioned, 
spinach,  Brussels  sprouts,  French  beans,  winter  cab- 
bage. Savoy  cabbage,  turnip  tops,  turnips,  and  celery. 
Potatoes  may  also  be  taken  in  moderate  quantities. 
Stewed  fruits,  or  baked  apples  or  pears,  may  with 
advantage  be  taken  every  day  at  one  meal,  and  a 
milk  pudding  made  with  rice,  sago,  and  tapioca  at 
the  other  meal.  Rhubarb  should  be  avoided  owing 
to  the  liability  of  the  calcium  oxalate  contained  in 
it  to  irritate  the  kidneys  during  its  excretion.  Rich 
pastry  and  all  rich  sweets  should  be  rigorously 
avoided  by  the  gouty. 

Nigld. — A  pint  of  hot  water,  flavoured  with  a 
slice  of  lemon  peel,  should  be  slowly  sipped  before 
retiring  to  bed. 

Alcohol. — As  regards  the  employment  of  alcohol, 
each  case  must  be  individually  and  carefully  dealt 
with.  During  an  attack  of  acute  gout  the  patient 
is  better  without  any  alcohol.  If  the  gouty  person 
be  of  robust  habit  of  body,  then  total  abstinence  is 
undoubtedly  the  best  for  such  a  patient.  If,  how- 
ever, the  cardiac  action  be  weak  and  failing,  then 


Alcohol  in  Gout.  225 

moderate  quantities  of  alcohol  should  certainly  be 
given.  In  cases  of  chronic  gout  a  moderate  amount 
of  alcohol  may  be  necessary  for  the  promotion  of 
digestion.  The  best  form  of  alcohol  for  the  gouty 
is  a  tablespoonful  of  matured  whisky  freely  diluted 
with  salutaris  water  or  with  plain  water,  and  taken 
towards  the  end  of  lunch  or  dinner.  If  any  w^ine 
is  taken  by  the  gouty,  those  which  are  least  open 
to  objection  are  light  but  sound  clarets  and  hocks. 
Old  wines  w^ith  a  fine  bouquet  are  very  provocative 
of  gouty  attacks  in  most  persons  predisposed  to  the 
disease,  probably  on  account  of  the  large  quantities 
of  ethereal  compounds  contained  in  them  power- 
fully affecting  the  metabolism  of  the  liver,  and  so, 
by  causing  an  increased  quantity  of  glycocine  to 
pass  from  the  liver  to  the  kidneys,  leading  to  an 
increased  production  of  uric  acid  in  the  last- 
mentioned  organs.  Ales  and  stout  should  also  be 
avoided  by  the  gouty. 


226 


•CHAPTER  XYI. 

Tlie  uses  of  mineral  waters  in  tlie  treatment  of  gout — The 
mineral  waters  best  suited  for  the  removal  of  gouty 
deposits — Classification  of  the  mineral  waters  used. 
ill  the  treatment  of  gout — The  simple  waters — Simple 
alkaline  water's — Alkaline  sulphated  waters — Alka- 
line muriated  waters — Commori  salt  or  muriated 
waters — Sulphur  waters — Hot  and  cold  mineral 
waters — Classification  of  mineral  ivaters  according 
to  their  therapeutic  value  in  the  treatment  of  the 
various  forms  of  gout. 

THE    USES   OF   MINERAL  WATERS   IN   THE   TREATMENT 

OF   GOUT. 

The  value  of  a  given  mineral  water  in  the  treat- 
ment of  gout  depends  greatly  on  the  main  object 
with  which  it  is  taken.  For  instance,  it  may  be 
taken  to  remove  gouty  deposits,  or  to  stimulate  the 
action  of  a  sluggish  liver  and  to  relieve  portal 
congestion,  or  for  the  treatment  of  gouty  dyspepsia, 
or  to  relieve  the  bowels  in  cases  of  torpor  and 
gastro-intestinal  catarrh,  or  to  act  on  the  kidneys, 
or  to  relieve  gouty  affections  of  the  skin.  Now  it 
is  manifest  that  any  one  mineral  water  is  not  likely 
to  produce  all  these  effects,  and  it  is  also  obviously 
conceivable  that  a  mineral  water  which  might  be 
most  useful  to  effect  one  of  these  purposes  might 


Uses  of  Mineral   Waters.  227 

prove  most  injurious  if  employed  to  effect  another. 
No  doubt  considerable  error  has  arisen  from  in- 
discriminately sending  gouty  patients  to  a  particular 
spa  without  giving  due  consideration  to  the  ques 
tion  as  to  whether  the  water  of  that  spa  is  suitable 
for  the  treatment  of  the  specific  gouty  disorder 
from  which  the  patient  is  suffering.  Moreover,  it 
is  well  to  bear  in  mind  that  a  patient  should  not  be 
sent  to  a  spa  during  the  acute  stage  of  gout,  nor  if 
suffering  from  marked  organic  disease  of  the  heart 
or  kidneys. 

The  use  of  a  mineral  water,  so  far  as  its 
employment  with  the  object  of  removing  gouty 
deposits  is  concerned,  lies  solely  in  its  watery  con- 
stituent, and  does  not  in  any  way  depend  on  the 
mineral  constituent  dissolved  in  it.  As  a  matter  of 
fact  the  salts  dissolved  in  a  great  many  of  the 
natural  mineral  waters  are  directly  harmful  in  gout 
both  by  encouraging  deposition  of  the  sodium 
biurate  and  by  checking  solution  of  the  gouty 
deposits.  The  flushing  of  the  system  of  a  gouty 
patient  with  abundant  quantities  of  water  is  un- 
doubtedly beneficial,  since  it  dilutes  the  blood  for 
the  time,  and  so  tends  to  prevent  uratic  precipita- 
tion, and  at  the  same  time  promotes  diuresis  and 
encourages  the  elimination  of  urates.  The  question, 
however,  naturally  arises  whether,  if  the  water  of  a 
mineral  water  be  its  only  beneficial  constituent  for 
effecting  the  removal  of  gouty  deposits,  the  sending 
of  gouty  patients  to  spas  for  such  a  purpose  pre- 
sents any  advantages  over  their  drinking  ordinar}^ 
water  at  home.     If  the  conditions  of  the  life  of  the 


228  The  Treatment  of  Gout. 

patient  at  home  and  at  a  spa  were  the  same,  there 
would  be  no  such  advantage,  but  among  the  special 
benefits  to  be  derived  from  residence  at  a  spa  must 
be  reckoned  the  almost  undistracted  attention  that 
is  given  b}^  the  patient  to  treatment,  the  careful 
dieting  that  is  frequently  observed,  the  change  of 
surroundincrs,  the  absence  of  business  or  home 
worries,  and  the  opportunities  for  the  use  of 
thermal  baths  for  the  external  treatment  of 
articular  gout.  It  should,  however,  be  carefully 
borne  in  mind  that,  owing  to  the  undoubted  fact 
that  sodium  salts  are  directly  detrimental  to  the 
removal  of  gouty  deposits,  those  springs  should  be 
avoided  which  owe  their  activity  to  those  salts, 
when  the  removal  of  the  deposits  is  the  main  object 
to  be  attained.  The  springs  which  contain  no 
sodium  salts,  or  traces  only,  are  the  ones  suitable 
for  such  cases — such  as  the  waters  of  Buxton,  Bath, 
and  Strathpeffer  in  Great  Britain :  in  France  the 
"waters  of  Aix-les-Bains,  Contrexeville,  and  Vittel ; 
in  Switzerland  the  Pfaefers  water ;  in  Austria  the 
Gastein  water ;  in  Bohemia  the  Teplitz  water ;  in 
Germany  the  Wildbad  water.  I  wish  it  to  be 
clearly  understood  that  I  am  by  no  means  con- 
demning the  very  proper  uses  to  which  mineral 
Avaters  containing  sodium  salts  can  be  put  for  the 
treatment  of  many  gouty  affections  of  the  viscera 
and  other  structures,  but  I  wish  to  emphasise 
the  point  that  when  the  system  is  flushed  with  a 
mineral  water  with  the  object  of  dissolving  and 
removing  gouty  deposits,  then  it  is  undoubtedly 
advisable  to  select  a  water  as  free  as  possible  from 


Uses  of  Mineral    IV.  i  teas.  229 

sodium  salts.  On  the  other  hand,  m  cases  of 
shiggish  action  of  the  hver,  of  gastro-intestinal 
catarrh  and  torpor,  of  gouty  dyspepsia,  and  of 
other  forms  of  irregular  gout  where  there  are  no 
appreciable  uratic  deposits  in  the  joints,  mineral 
waters  .  containing  sodium  salts  are  undoubtedly 
beneficial,  owing  to  the  action  of  those  salts  as 
hepatic  and  gastro-intestinal  stimulants. 

The  explanations  given  as  to  the  modus 
operandi  of  a  particular  mineral  water  must 
sometimes  be  received  Avith  a  certain  amount  of 
caution.  For  instance,  the  advocates  of  one  mineral 
water  will  extol  its  efficacy  in  the  treatment  of 
gout  on  account  of  the  lime  salts  contained  in  it 
and  its  freedom  irom  sodium  salts,  whilst,  on  the 
other  hand,  the  advocates  of  another  mineral  water 
Avill  insist  that  the  large  quantities  of  sodium  salts 
present  in  it  and  the  absence  of  lime  salts  are  the 
potent  factors  in  its  usefulness  in  the  treatment  of 
gout.  The  advantages  and  disadvantages  of  sodium 
salts  have  already  been  referred  to.  With  regard 
to  the  presence  of  lime  salts,  a  mineral  water  con- 
taining such  does  not  exercise,  by  virtue  of  those 
lime  salts,  either  a  deleterious  or  a  beneficial  action 
on  the  gouty  deposits  of  sodium  biurate.  The  only 
objection  to  a  water  containing  a  large  quantity  of 
lime  salts  is  the  tendency  to  produce  digestive 
disturbances  and  to  cause  constipation. 

CLASSIFICATIOX   OF   MINERAL   WATERS. 

The  various  mineral  waters  used  in  the  treat- 
ment   of   gout    may   be    classified    according    to 


230 


The  Treatment  of  Gout 


their  chemical  composition  into  the  six  following 
groups : — 

1.  The  simple  waters,  or  waters  comparatively 
free  from  sodium  salts. 

2.  The  simple  alkaline  waters. 

3.  The  alkaline  sulphated  waters. 

4.  The  alkaline  muriated  waters. 

5.  The  connnon  salt  or  muriated  waters. 
G.  The  sulphur  waters. 

THE    SIMPLE     WATERS,    OR    WATERS    COMPARATIVELY 
FREE    FROM    SODIUM    SALTS. 

These  are  the  waters  that  are  especially  likely 
to  prove  useful  for  the  removal  of  uratic  deposits  in 
the  joints  and  tissues.  They  contain  small  propor- 
tions of  calcium  carbonate  and  calcium  sulphate, 
but  the  quantities  of  sodium  salts  present  are  so 
small  that  for  all  practical  purposes  they  may  be 
neglected.  The  following  table  (Table  LVIII.)  shows 
the  proportions  of  sodium  salts  in  the  respective 
waters  of  this  class,  represented  as  grains  of  sodium 

per  gallon : — 

TABLE    LVIII. 

Shorring  the  proportioyif  of  sodium  talts,    represented  as   grains  of 
sod'cnn  per  [laJlon,  in   the  principal  simple  waters. 


Mineral  water. 

Grains  of  sodium 
per  gallon. 

Teplitz 
Strathpoffcr . . . 

0'20 
0-15 

Contrexcvillo 

0-79 

Aix-les-Bains 

1-34 

Buxton 

1-47 

Pf  acf  ors 

1  61 

Gastein 

5-89 

Wildb.'id       ... 

7-63 

Bath 

9-42 

Vittel 

12-39 

The  Simple   Waters.  231 

Teplitz  (Bohemia).  The  waters  are  hot  (83^  to 
114^  F.).  Altitude  about  730  feet.  Thermal  baths 
and  peat  baths  are  provided.  Open  all  the  year, 
but  the  usual  season  is  from  May  to  September. 

Strathpeffer  (Scotland,  Ross-shire).  The  waters 
are  cold.  Altitude  about  200  feet.  Strathpeffer 
also  possesses  sulphur  springs  and  a  chalybeate 
spring.  Various  kinds  of  baths  are  provided.  The 
sulphur  waters  are  useful  in  the  treatment  of  the 
various  skin  affections  connected  with  gout.  Open 
all  the  year,  but  the  usual  season  is  from  May  to 
October. 

Contrexeville  (France).  The  waters  are  cold. 
Altitude  1,150  feet.  Baths  are  provided.  The  water, 
in  addition  to  being  almost  free  from  sodium  salts, 
contains  magnesium  sulphate,  so  that  it  is  useful 
not  only  for  the  removal  of  uratic  deposits,  but  also 
in  the  treatment  of  gastro-intestinal  and  hepatic 
disorders  associated  with  gout,  and  for  the  treat- 
ment of  urinary  gravel.  The  season  is  from  the 
becrinninor  of  June  to  the  end  of  October. 

Aix-les-Bains  (France).  The  waters  are  hot 
(112°  F.).  Altitude  870  feet.  The  waters  contain 
free  sulphuretted  hydrogen.  This  spa  is  especially 
known  for  its  baths,  douches,  and  douche-massage, 
all  of  which  methods  of  treatment  are  most  bene- 
ficial in  the  removal  of  the  stiffness  and  sweUing  of 
the  joints  left  after  an  attack  of  gout.  The  waters 
are  also  employed  in  the  treatment  of  cutaneous 
affections  connected  with  gout.  Sir  Alfred  Garrod 
especially  recommends  the  treatment  at  Aix-les- 
Bains   in   cases   of  chronic  gout  accompanied  b}' 


232  The  Treatment  of  Gout. 

indolent  swelling  of  the  previously  inflamed  part, 
and  by  eczema.  The  spa  is  open  all  the  year,  but 
the  season  lasts  from  April  to  November. 

Buxton  (England,  Derbyshire).  The  waters  are 
warm  (82°  F.).  Altitude  1,000  feet.  Baths,  douches, 
and  douche-massage  are  provided.  The  water 
contains  a  considerable  amount  of  free  nitrogen. 
On  account  of  the  very  small  proportion  of  sodium 
salts  present  it  is  an  extremely  beneficial  water 
to  employ  with  the  object  of  removing  uratic 
deposits.  The  climate  is  bracing.  Open  all  the 
year,  but  the  season  is  from  April  to  September. 

Pfaefers  (Switzerland).  The  waters  are  warm 
(89°  to  93'  F.).  Altitude  about  1,700  feet.  Baths 
are  provided.     The  season  is  from  May  to  October. 

Gastein  (Austria).  The  waters  are  hot  (78°  to 
121°  F.).  Altitude  3,310  feet.  Baths  are  provided. 
The  season  is  from  the  beginning  of  May  to  the 
end  of  September. 

Wildbad  (Germany).  The  waters  are  hot  (91° 
to  105°  F.).  Altitude  about  1,320  feet.  Baths, 
douches,  and  electric  baths  are  provided.  The 
season  is  from  the  beginning  of  Ma}"  to  the  end  of 
September. 

Bath  (England,  Somersetshire).  The  waters  are 
hot  (104°  to  120°  F.).  Altitude  100  feet.  Excellent 
baths,  douches,  and  douche-massage  are  provided. 
The  water  is  a  very  useful  one  to  employ  with  the 
object  of  removing  uratic  deposits,  and  chronic 
affections  of  the  joints  can  be  well  treated  at  Bath 
by  external  methods.  Open  all  the  year,  but  the 
spring  and  autumn  are  the  favourite  seasons.     The 


Simple  Alkaline   Waters.  233 

climate  of  Batli  is  mild,  and  it  is  therefore  a  good 
Avinter  resort. 

Vittel  (France).  The  waters  are  cold.  Altitude 
1,100  feet.      The  season  is  from  May  to  September. 

SIMl'LE    ALKALINE    WATERS. 

These  waters  contain  sodium  bicarbonate.  They 
are  useful  for  gouty  patients  suffering  from  hepatic 
congestion,  dyspepsia,  and  gastro-intestinal  catarrh. 
The  principal  waters  of  this  class  are  those  of 
Yichy,  Vals,  Xeuenahr,  Salzbrunn,  Fachingen,  and 
Bilin. 

Vichy  (France).  The  waters  are  hot  (89^  to 
110°  F.).  Altitude  736  feet.  Baths  are  provided. 
The  waters  are  especially  useful  in  the  treatment 
of  gouty  dyspepsia  and  gastro-intestinal  catarrh, 
in  cases  of  deranged  hepatic  function,  and  for 
plethoric  gouty  patients  suffering  from  glycosuria 
or  diabetes.  Open  all  the  year,  but  the  season 
is  from  the  middle  of  May  to  the  end  of  Sep- 
tember. In  the  middle  of  summer  Vichy  is 
very  hot. 

Vals  (France).  The  waters  are  cold.  Altitude 
300  feet.  The  waters  may  be  used  for  the  same 
class  of  gouty  cases  as  mentioned  in  connection 
with  the  Yichy  waters,  but  those  springs  containmg 
iron  should  be  avoided  by  gouty  patients.  The 
season  is  from  the  middle  of  May  to  the  middle 
of  October. 

Neuenahr  (Germany).  The  waters  are  hot  (75^ 
to  10-i°  F.).  Altitude  760  feet.  Baths  are  provided. 
The  waters  may  be  used  for  the  same  class  of  gouty 


234  The  Treatment  of  Gout. 

cases  as  mentioned  in  connection  Avith  the  Yichy 
waters.  The  season  is  from  May  to  October,  but  in 
the  middle  of  the  summer  Neuenahr  is  very  hot. 

Salzbrunn  (Prussian  Silesia).  The  waters  are 
cold.  Altitude  1,320  feet.  The  waters  may  be 
used  for  the  same  class  of  gouty  cases  as  men- 
tioned in  connection  with  the  Vichy  waters.  The 
season  is  from  the  beginning  of  May  to  the  end  of 
September. 

ALKALINE    SULPHATED   WATERS. 

These  waters  contain  sodium  bicarbonate, 
sodium  sulphate,  and  generally  a  moderate  pro- 
portion of  sodium  chloride.  They  are  useful  in 
the  treatment  of  gout  connected  with  congestion 
of  the  liver  and  portal  system,  and  of  gout  con- 
nected with  gastro-intestinal  catarrh  and  with 
some  forms  of  dyspepsia.  They  may  also  be  em- 
ployed in  the  treatment  of  gouty  glycosuria.  The 
principal  waters  of  this  class  are  those  of  Carls- 
bad, Marienbad,  Tarasp-Schuls,  Brides-les-Bains, 
Cheltenham,  Leamington,  and  Bertrich. 

Carlsbad  (Bohemia).  The  Carlsbad  waters  are 
rich  in  sodium  sulphate  and  sodium  bicarbonate, 
and  also  contain  a  moderate  proportion  of  sodium 
chloride.  The  waters  are  hot  (OS""  to  162°  R). 
Altitude  1,1  GO  feet.  Baths  are  provided.  The 
waters  are  best  suited  for  gouty  patients  suffering 
from  torpor  of  the  hepatic  and  gastro-intestinal 
functions,  and  especially  for  cases  of  congestive 
enlargement  of  the  liver  with  a  tendency  to 
haemorrhoids.     They  are  also  of  use  in  the  treat- 


Alkalixe  Sulpha  ted   Waters.        235 

merit  of  gouty  glycosuria.  The  Avatcrs  are  best 
suited  for  those  of  fairly  robust  constitutions. 
They  are  contra-indicated  if  heart  disease  is 
present,  or  if  arterio-sclerotic  changes  are  ad- 
vanced, or  if  the  kidneys  are  seriously  implicated. 
The  season  is  from  the  middle  of  April  to  the 
end  of  September.  A  course  at  Carlsbad  may 
advantageously  be  succeeded  by  a  stay  in  Switzer- 
land at  a  station  situated  at  a  high  altitude. 

Marienbad  (Bohemia).  The  waters  are  cold. 
Altitude  about  1,980  feet.  Baths  are  provided. 
The  waters  are  very  similar  in  composition  to 
those  of  Carlsbad,  and  are  useful  for  the  same 
class  of  cases.  The  season  is  from  May  to  Sep- 
tember. A  course  at  Marienbad  is  also  advan- 
tageously succeeded  by  a  stay  at  a  high  altitude. 

Tarasp-Schuls  (Switzerland).  The  waters  are 
cold.  Altitude  3,870  feet.  Baths  are  provided. 
The  Avaters  are  useful  for  the  same  class  of  cases  as 
mentioned  in  connection  with  the  Carlsbad  waters. 
The  season  is  from  the  middle  of  June  to  the 
middle  of  September. 

Brides-les-Bains  (France).  The  waters  are 
hot  (95°  F.).  Altitude  about  1,860  feet.  Baths 
are  provided.  The  waters  are  useful  for  the  treat- 
ment of  gouty  dyspepsia  associated  with  con- 
stipation. The  season  is  from  the  beginning  of 
June  to  the  end  of  September. 

Cheltenham  (England,  Gloucestershire).  The 
waters  are  cold.  The  non- chalybeate  waters  are 
useful  in  the  treatment  of  congestive  conditions  of 
the  liver  associated  w^ith  gout. 


2^6  The  Treatmext  of  Gout. 

Leamington  (England,  Warwickshire).  The 
waters  are  cold.  Baths  are  provided.  The  waters 
are  useful  in  the  treatment  of  torpid  conditions  of 
the  hver  and  of  the  gastro-intestinal  tract  asso- 
ciated with  gout,  and  also  in  the  treatment  of  gouty 
glycosuria, 

ALKALINE    MUPJATED    WATERS. 

These  waters  contain  sodium  bicarbonate  and 
sodium  chloride.  They  are  useful  in  the  treatment 
of  gouty  dyspepsia  and  of  gouty  catarrhal  affections 
ot"  the  respiratory  organs.  The  principal  waters  of 
this  class  are  those  of  Ems,  Royat,  Assmannshausen, 
and  La  Bourboule. 

Ems  (Germany).  The  waters  are  hot  (80°  to 
120^  F.).  Altitude  300  feet.  Baths  are  provided. 
The  waters  are  especially  useful  for  patients  suffer- 
ing fi'om  gouty  bronchitis  and  asthma,  for  the 
treatment  of  which  affections  the  waters  can  be 
inhaled  in  a  finely  divided  condition.  They  may 
also  be  employed  in  the  treatment  of  gouty  dys- 
pepsia. The  climate  is  a  relaxing  one,  and  is  best 
suited  to  elderly  gouty  patients. 

Royat  (France).  The  waters  are  warm  (68°  to 
95'-'  F.).  Altitude  1,480  feet.  Baths  are  provided. 
The  waters  are  useful  for  the  same  class  of  cases  as 
mentioned  in  connection  with  the  Ems  waters. 
The  season  is  from  the  middle  of  May  to  the 
middle  of  September. 

Assmannshausen  (Prussia).  The  water  is  tepid 
(82°  F.),  and  contains  a  small  proportion  of  lithium 
bicarbonate. 


MURIA  TED     I  Va  TERS.  23/ 

La  Bourboule  (France).  The  water  is  hot 
(130^  F.).  Altitude  2,780  feet.  Baths  are  provided. 
The  waters  arc  arsenical  as  well  as  alkaline 
inuriated,  and  may  be  useful  in  certain  cases  of 
chronic  gouty  skin  disorders.  The  season  is  from 
the  beginning  of  Jime  to  the  end  of  September. 

COMMON    SALT    OR   MURIATED   WATERS. 

These  waters  contain  sodium  chloride  as  their 
principal  constituent,  and  some  of  them  also  con- 
tain a  large  amount  of  free  carbonic  acid  gas. 
They  are  of  use  in  the  treatment  of  gastro-intestinal 
and  hepatic  gout,  especially  when  accompanied  by 
constipation,  and  in  cases  of  gouty  dyspepsia  asso- 
ciated with  general  atony.  They  exercise  a  stimu- 
lant effect  on  the  gastric  glands  and  on  the  liver 
cells.  They  are  not  indicated  in  cases  of  articular 
gout,  when  the  removal  of  the  uratic  deposits  is  the 
main  object  of  treatment.  The  principal  waters  of 
this  class  are  those  of  Homburg,  Wiesbaden,  Kis- 
singen,  Baden-Baden,  Nauheim,  Llandrindod,  Wood- 
hall  Spa,  Llangammarch  Wells,  Oeynhausen. 

Hornburg  (Germany).  The  waters  are  cold. 
Altitude  about  600  feet.  Baths,  massage,  and 
electrical  treatment  are  provided.  The  waters 
produce  slight  purgation  and  diuresis,  and  are 
useful  for  the  treatment  of  gouty  d3^spepsia  with 
a  tendency  to  constipation,  and  of  gouty  gastro- 
intestinal catarrh  and  hepatic  congestion  associated 
with  general  atony. 

Wiesbaden  (Germany).  The  waters  are  hot 
(100^  to  150^  F.).     Altitude  380  feet.      Baths  are 


238  The   Treatment  of  Gout. 

provided.  The  waters  are  useful  for  the  same  class 
of  cases  as  mentioned  in  connection  with  the 
Homburg  waters,  but  should  be  avoided  in  cases 
of  articular  gout.  Open  throughout  the  year,  but 
in  midsummer  Wiesbaden  is  very  hot. 

Kissingen  (Basraria).  The  waters  are  cold. 
Altitude  about  600  feet.  Baths  are  provided.  The 
waters  are  useful  for  the  same  class  of  cases  as 
mentioned  in  connection  with  the  Homburg  waters. 
The  season  is  from  May  to  the  end  of  September. 

Baden-Baden  (Grand  Duchy  of  Baden).  The 
waters  are  hot  (120^  to  150^  F.).  Altitude  about 
650  feet.  Baths,  douches,  and  electric  baths  arc 
provided.  The  waters  are  useful  in  the  treatment 
of  gastro-intestinal  catarrh  and  sluggish  conditions 
of  the  liver.  Open  all  the  year,  but  the  sea- 
son is  from  the  beginning  of  May  to  the  end  of 
October.  During  July  and  the  first  half  of  August 
Baden-Baden  is  very  hot. 

Nauheim  (Germany).  The  waters  are  warm 
(82°  to  95=  F.).  Altitude  about  400  feet.  This  spa 
is  specially  known  for  its  baths  in  connection  with 
the  treatment  of  various  affections  of  the  heart. 
Two  of  the  waters  are  somewhat  similar  in  com- 
position to  the  Homburg  water,  and  may  be  em- 
ployed in  the  treatment  of  gouty  dyspepsia.  The 
season  is  from  May  to  the  end  of  September. 

Llandrindod  (Wales,  Radnorshire).  The  waters 
are  cold.  Altitude  700  feet.  Baths  are  provided. 
Muriated  waters,  sulphur  waters,  and  weak  chaly- 
beate waters  are  iound  at  Llandrindod.  The 
muriated   waters   are   useful    in  the  treatment  of 


5  ULPHUR     Wa  TE  A'S.  239 

gouty  gastro-intestinal  catarrh  and  congestion  of 
the  liver,  and  also  in  the  treatment  of  gouty 
glycosuria.      The  season  is  from  May  to  October. 

Woodhall  Spa  (England,  Lincolnshire).  This 
water,  in  addition  to  being  a  highly  muriated  water, 
contains  bromides  and  iodides. 

Llangammarch  Wells  (Wales,  Brecknockshire). 
Altitude  about  600  feet.  This  water,  in  addition  to 
being  a  muriated  water,  contains  a  small  quantity 
of  barium  chloride. 

Brine  Baths.  The  brine  baths  of  Droitwich 
(England,  Worcestershire),  Kreuznach  (Germany), 
Ischl  (Austria),  Rheinfelden  (Switzerland),  Aussee 
(Styria),  Reichenhall  (Bavaria),  and  Bourbonne-les- 
Bains  (France)  are  usefid  in  the  treatment  of  stiff- 
ness and  thickening  of  the  joints  in  cases  of  chronic 
articular  gout,  but  should  be  avoided  if  gouty  skin 
affections  are  present. 

SULPHUR   WATERS. 

These  waters  contain  sulphur,  either  in  the  form 
of  sulphuretted  hydrogen  only,  or,  in  addition  to 
free  sulphuretted  hydrogen,  some  of  them  contain 
combined  sulphur  in  the  form  of  the  sulphides  of 
calcium,  magnesium,  and  sodium.  They  are  fre- 
quently very  useful  in  the  treatment  of  gouty  skin 
affections,  especially  eczema  and  psoriasis.  Sulphur 
baths  are  also  of  benefit  for  the  same  purpose.  In 
addition,  the  Harrogate  waters  may  be  employed  in 
the  treatment  of  gouty  gastro-intestinal  and  hepatic 
affections.  The  sulphur  springs  may  be  classified 
into  the  cold  and  hot  springs. 


240 


The  Treatment  of  Gout. 


Cold  sulphur  springs. — The  principal  waters 
of  this  class  are  those  of  Harrogate  (England, 
Yorkshire),  Strathpeffer  (Scotland),  Llandrindod 
(Wales,  Kadnorshire),  Gurnigel  (Switzerland;, 
Heustrich  (Switzerland),  Nenndorf  (Prussia),  and 
Weilbach  (Germany). 

Hot  sulphur  springs. — The  principal  waters  of 
this  class  are  those  of  Aix-les-Bains  (France),  Aix- 
la-Chapelle  (Germany),  Baden  (Switzerland),  Baden 
(near  Vienna),  Uriage  (France),  Bagneres-de-Luchon 
(France),  Allevard  (France),  Saint-Honore  (France), 
and  Schinznach  (Switzerland). 

HOT   AND   COLD   MINERAL   WATERS. 

The  following  table  (Table  LIX.)  shows  a  classi- 
fication of  the  various  mineral  waters  used  in  the 
treatment  of  gout  into  hot  and  cold  waters  : — 

TAIiLE    LIX. 

Classification    of  the   various  mineral  ivaters  used  in  the  treatment 
of  gout  into  hot  and  cold  waters. 


Hot. 

Cold. 

Aix-les-Bains 

Cheltenham 

Aix-la-Chapelle 
Baden 

Contrexeville 
Harrogate 

Baden-Baden 

Homburg 

Bith 
Brides-les-Bains 

Kiss  in  gen 
Leamington 

Buxton 

Llandrindod 

Carlsbad 

IMarienbad 

Kins 

Salzbrimn 

(iastein 

La  l>oxnboule 

Strathpelier 
Tarasp-Schuls 

Nauheim 

Yals 

Xeucnahr 
Kagatz-Pfaefers 

Yichv  (some  spi-ings) 
Vittel 

Koyat 
Teplitz 

' 

Vichy  (some  spiings) 
Wiesbaden 

Wildli.ul 

Uses  of  Mineral    Waters. 


241 


THERAPEUTIC    USES   OF   THE    VARIOUS   MINERAL 
WATERS  FOR  THE  DIFFERENT  FORMS  OF  OOUT. 

In  the  following  table  (Table  LX.)  the  various 
mineral  waters  are  classified  according  to  their 
therapeutic  value  in  the  treatment  of  the  various 
forms  of  gout. 

TABLE    LX. 

Classijicatioii    of   the   various    mineral    waters    according    to     their 
therapeutic  value  in  the  trea>nent  of  the  various  forms  of  gout. 


Object  of  taking  the 
water. 


The  waters  best  suited  for  the  purpose. 


Absorption  of  gouty     Aix-les-Bains,  Bath,  Buxtou,  Contrexeville, 
deposits  from  the  Gastein,  Pfaefers,    Strathpeffer,  Teplitz, 

joints  and  tissues.  Vittel,  Wildbad. 


Treatment  of  gouty      Brides-les-Bains,  Carlsbad,  Ems,  Homburg, 
dyspepsia.  Kissingeu,  Xeuenahr,  Koyat,  Yals,  Vichy, 

Wiesbaden. 


Treatment  of  gouty 
congestion  and 
torpor  of  the  liver, 
and  of  gastro-in- 
testinal  catarrh 
and  torpor. 


Treatment  of  gouty 
affections  of  the  re- 
spiratory organs. 


Baden-Baden,  Boiu-bonne,  Carlsbad.  Chel- 
tenham, Contrexeville,  Harrogate,  Hom- 
burg, Kissingen,  Leamington,  Llan- 
drindod,  Marienbad,  Xeuenahr,  Tarasp- 
Schuls,  Vals,  Vichy,  Vittel,  Wiesbaden. 


Ems,  Royat. 


Treatment  of  gouty 
glycosuria  and 
diabetes. 


Treatment  of  gouty 
skin  affections. 


Carlsbad,  Contrexeville,  Kissingen,  Lea- 
mington, Llandriudod,  Marienbad 
Xeuenahr,  Yals,  Vichy,  Vittel. 


Sulphur  waters   and  baths   [see  pp.  239, 
240j. 


Q 


t. 


<)  Lc/yv*>Tv_-A.^-'V-«v 


INDEX. 


Abarticular  £,'oiit,  114-124 
Acidity  and  gout,  190-193 
Acne,  Gouty,  123 
Acute  gout,  107-110 

,  Clinical  features  of,  107-110 

,  Diet  in,  204,  205 

,  Symptoms  of,  IDS,  109 

,  Treatment  of,  201-205 

etiology  of  gout,  105-107 
Age  and  gout,  105 
Aix-la-Chapelle  waters,  240 
Aix-les-Bains  waters,  231,  240,  241 
Albuminuria,  Treatment  of,  210,  211 
Alcohol  and  gout,  145-149,  224,  225 
Alkalies  and  gouty  deposits,  180-190 

,  Treatment  of  gout  by,  17G-192 

Alkaline  niuriated  waters,  236,  237 

sulpliated  waters,  234-230 

waters,  233,  234 

Alkalinitv  of  blood  of  gout,  129-131, 

189 
Allevard  waters,  240 
Alloxur  bases  and  gout,  9,  10 
Amido  bodies  and  uric  aci'l,  (58,  69 
Amorphous  quadriurates,  7 

urate  deposit,  84-86 

Ana'mia,  Uric  acid  in  blood  of,  48 
Angina  ]iectoris,  Treatment  of,    215, 

216 
Anginal  attacks.  Treatment  of,  214 
Animal  diet  and  uric  acid,  65,  66 
Asparagus  ash,  Effect  of,  152 
Assinannshausen  waters,  236 
Asthma,  Gouty,  US 

,  Treatment  of,  236 

Aussee  baths,  239 


Baden-Baden  waters,  238,  241 

Baden  waters,  240 

Bagneres-de-Luchon  waters,  240 

Bath  waters,  232,  241 

Baths,  Thermal,  211 

Beers,  Aeidity  of,  146 

Beers  and  gout,  145-149 

,  Gout-inducing    power  of,    140, 

148,  140 
Beetroot  ash,  Effect  of,  154 
Birds,  Urinary  excrement  of,  S3,  84 
Biurate,  Causes  of  deposition  of,  92- 

100 

,  Gelatinous  form  of,  88 

,  yolubility  in  serum  of,  92 


Biurates,  Composition  of,  2 
Bladder,  Irritability  of,  121 
Blood,  Detection  of  uric  acid  in,  31-34 

disorders  and  uric  acid,  48 

,  Estimation  (if  uiic acid  in,  31-34 

,  Introduction  of  uric  acid  into, 

25,  82 

of  birds,  Examination  of,  44,  45 

of  gout,  Alkalinity  of,  129-131, 

139 

of  mammals,  Examination  of,  44 

of  man.  Examination  of,  43,  44 

of  reptiles.  Examination  of,  45 

,  Uric  acid  compnund  in,  2 

,  Uric  acid  not  normal  constituent 

of,  43-47 
Boils  and  gout,  123 
Bourbonne-les-Bains,  239 
Bridesdes-Bains  waters,  235,  241 
Brine  baths,  239 
Bronchitis,  Gouty,  117,  118 

,  Treatment  of,  236 

Brussels  sprouts  ash.  Effect  of,  152 
Buxton  waters,  232,  241 


c 


Cabbage  ash.  Effect  of,  154 
Calculi,  Treatment  of  renal,  218 

,  Uric  acid,  121 

Carbuncles,  Gouty,  123 
Cardiac  irritability,  IIS 
Carlsbad  waters,  234,  235,  241 
Carrot  ash,  Effect  of,  155 
Cartilage,  Uratic  deposition  in,  90,  91 
Cauliflower  ash,  Effect  of,  156 
Causation  of  gout,  5-24 
Celery  ash,  Effect  of,  154 
Cheltenham  waters,  235,  241 
Chronic  deforming  gout.  111 
Chronic  gout,  110-113 

';  Treatment  of,  20S-212 

,  Urine  of,  112 

Colchicum,  Action  of,  205-208 

and  uric  acid  excretion,  206,  207 

in  gnut,  202,  203 

Cold  mineral  waters,  240 
Common  salt  and  gout.  174 
Conclusions  as  to  pathology  of  gout, 

103,  104 
Connective    tissues    and    uric    acid 

formation,  40,  41 
Constipation,  Treatment  of,  203,  204, 

233-239 
Contrexeville  waters,  231,  241 
Cycling  and  gout,  212 


244 


Gout. 


D 


Deafness,  Gouty,  124 

Detection  of  uric  acid  in  blood,  31-34 

Diabetes,  Gouty,  123 

,  Mineral  waters  for,  241 

,  Treatment  of,  219,  220 

Diagnosis  of  gdut,  126,  127 

Diet  and  uric  acid  exeretiou,  65-li7 

formation,  65,  66 

in  acute  gout,  204,  205 

in  gout,  204,  205,    222-225 

Distinction  of  gout  from  rheumatism, 

126 
rlieumatoid     arthritis, 

126,  127 
Droitwich  batlis,  239 
Dyspepsia,  Gouty,  117 

,  Mineral  waters  for,  241 

,  Treatment  of,  233,  234,  236,  237 


E 


Ear,  Gouty  deposits  in,  101 
Ebstein's    views     and     experiments, 
11-18 

• ,  (Criticism  of,  14,  10,  17 

Eczema,  Goutv,  122 

,  Treatment  of,  218,  239 

Ems  waters,  23(1,  241 

Epilepsy  and  gout,  120 

Estimation  of  uric  aciil  in  blood,  31-34 

urine,  29-31 

Exciting  causes  of  gout,  106 
Exercise  and  gout,  212 


Fibroid  tissue  degeneration  and  gont, 

19 
Flesh  diet  and  uric  acid,  65,  66 
Flying  gout,  124 
French  beans  ash,  Effect  of,  153 


G 


Gastein  waters,  232,  241 
Gastrointestinal  catarrh.  Gouty,  117 

,  Mineral  waters  for,  241 

,  'I'reatment  of,  233,  234,  237, 

239,  241 

torpor.  Mineral  waters  for,  241 

Glyoocine   and   nric  acid   fonuation, 

68-71 
Glycosuria,  Gouty,  123 

,  Mineral  waters  for,  241 

,  Treatinent  of,  219,  220,  233,  234 

Gout,  Abarlicular,  114-124 

,  Acule,  107-110 

,  ylCtiology  of,  105-107 

,  Alkalinity  of  blood  of,  129-131, 

139 

and  alcohol,  14.'5-149 

and  deficient    excretion  of  uric 

acid,  26-28 

and  kidney  affections,  52-03 

anil  nervous  system,  21-23 

and  nitrogenous  diet,  140,  141 


Gout  and  iheumatism,  Distinction  of, 
126 

and  rhetunatoid  arthritis,  Dis- 
tinction of,  126,  127 

and  uratic  deposition,  5,  6 

and  vegetables,  144,  150-175 

,  Author's  view  of  cause  of,  24 

,  Causation  of,  5-24 

,  Cause  of  heredity  of,  62 

,  Chronic,  110-133 

,  Chronic  deforming,  111 

,  Clinical  features  of,  107-125 

,  Conclusions  as  to  jiathology  of, 

103,  104 

,  Definition  of,  1 

,  Diagnosis  of,  126,  127 

,  Diet  in,  204,  205,  222-225 

,  Diet  in  acute.  204,  205 

,  Disfinction  of  rheumatism  from, 

126 
, rheumatoid  arthritis 

from,  126,  127 

,  Exciting  causes  of,  106 

,  Forms  of,  107-125 

,  Humoral  theory  of,  4 

in  the  liver,  124 

,  Irregular,  114-124 

,  • — -,  Causation  of,  6,  7 

,  Metastatic,  124,  125 

,  Pathology  of,  1-104 

,  Predisposing  causes  of,  105-107 

,  Preventive  treatment  of,  220,  221 

,  Primary  cause  of  53 

,  Prognosis  of,  127 

,  Renal  oiigin  of,  60-63 

,  Retrocedent,  124,  125 

,  Suppressed,  114 

,  Symj'toms  of  acute,  108,  109 

— .  chronic,  110-113 

,  Tophaceous,  111 

,  Toxic  agents  causing,  59,  60 

,  Treatment  of,  199-241 

,  acute,  201-205 

,  chronic,  208-212 

,  subacute,  208,  209 

,  Various  forms  of,  107-125 

Gouty  acne,  123 

asthma,  118 

bronchitis,  117,  118 

cardiac  irritability,  118 

deafness,  124 

deposits.  Formation  of,  86-89 

,  Mineral  waters  for,  241 

,  Treatment  of,  230-233,  241 

diabetes,  123 

,  Treatment  of,  219,  220,  233 

dyspepsia,  117 

eczema,  122 

gastro-intestinal  catarrl),  117 

glycosuria,  123 

— ,  Treatment  of,  219,  220,  233, 

234 

heart,  Treatment  ff,  215 

hepatic  congestion,  124 

herpes,  122 

insomnia,  120 

joints.   Treatment   of,    201,    202, 

209-212,  2.30-233 

kidney,  120,  121 

,  Signs  of.  2'-0 

and  heart  112,113 


Index. 


245 


Gouty  laryngitis,  117 

migraine,  119 

neuralgia,  119 

neui-itis,  119,  120 

,  Treatment  of,  217 

oesopliagismus,  110 

orcliitis,  125 

parotitis,  125 

paroxysm,  Cause  of,  101-103 

,  Treatment  of,  201,  202 

pharyngitis,  1U'> 

phlebitis,  118,  119 

,  Treatment  of,  21(5,  217 

prurigo,  123 

pruritus,  123 

psoriasis,  123 

pulmonary  congestion,  IIS 

sciatica,  119 

'-,  Treatment  of,  217 

tracheitis,  117 

urticaria,  123 

vertigo.  Treatment  of,  214 

Go^vland-Hopkins'  jirocess,  30,  31 
Granular  disease  of  kidneys  and  gout, 

55-57 
Gravel,  Uric  aciil,  121 
Great  toe  and  gout,  101 
Green-peas  ash,  Effect  of,  150 
Guaiacum  in  gout,  20S,  221 
Guruigel  waters,  210 


H 

Harrogate  waters,  239,  240,  241 
Heart  and  gouty  kidney,  112,  113 

irregular  gout,  IIS 

,  Treatment  of  gouty,  215 

Hepatic  congestion,  Goutv,  124 

,  Treatment  of,  233,  234,  237. 

239 

derangements  and  gout,  71,  72 

Hereditary  factor  of  gout,  •32 
Heredity  and  gout,  105,  10(3 
Herpes,  Gouty,  122 
Heustrich  waters,  240 
Homburg  waters,  237,  241 
Hot-air  baths,  212 

mineral  waters,  240 

Humoral  theoiy  of  gout,  4 
Hypoxanthin,  73 


Inherited  gout.  Cause  of,  62 
Insomnia  and  gout,  120 

,  Treatment  of,  204 

Irregular  gout,  114-124 

,  Causation  of,  6,  7 

,  Treatment  of,  214,  220 

Irritability  of  bladder,  121 
Irritable  t^emper,  Treatment  of,  219 


Joints,  Causes  of  uratic  deposition  in, 
98-101 


Joints,  Gouty,  98-101 

,  Treatment  of  gouty,  201,  202, 

209-212,  230-233 


K 


Kidney  affection  causing  gout,  Nature 

of,  62 

affections  and  gout,  52-63 

disease  and    uratic    deposition, 

54-57 

,  Treatment  of,  210,  211 

,  Gouty,  120,  121 

,  Signs  of  gouty,  200 

Kidneys  and  uric  acid  formation,  37, 

38 

,  Excretion  of  uric  acid  bj-,  53 

in  chronic  gout,  111,  112 

Kissingen  waters,  238,  241 
Kreuznach  baths,  239 


La  Bourboule  waters,  237 

LarATigitis,  Goutv,  117 

Lead  gout,  113,  114 

Lead  poisoning  and  gout,  59,  60,  9Q>, 

97 

uric  acid,  50 

Leamington  waters,  236,  241 
Lettuce  ash.  Effect  of,  153 
Leucocvthfemia,  Uric  acid  in  blood 

'  of,  4S 
Leucocytosis  and  uric  acid,  74-77 
Lithium      carbonate,      Experiments 

with,  179-181,  183,  187-189 
citrate,  Experiments  with,   179, 

ISO,  184 
salts  and   gouty  deposits,   183, 

184,  187-189 
Liver  affections.  Mineral  waters  for, 

241 

and  uric  acid  formation,  38-40 

derangements  and  gout,  71,  72 

disease  a  ad  uric  acid  formation, 

71,  72 

,  Gout  in  the,  124 

Llandriiidod  waters,  238,  240,  241 
Llangam march  Wells,  239 
Lysidine,  Effect  of,  180,  186 
,  Experiments  with,  179,  ISO,  186 


M 

Marienbad  watex's,  235,  241 
Massage  and  gout,  211 
Mental  depression  and  gout,  120 
Metastatic  gout,  124,  125 

,  Treatment  of,  213,  214 

Migraine,  Gouty,  119 

Mineral  waters,  Alkaline  muriated, 

236,  237 
.  Alkaline    sulphated,    234, 

236 
,  Classification  of,  229,  230, 

240,  241 
,  Cold.  240 


24^ 


Gout. 


Mineral  waters  for  gastro-intestinal 

catarrh,  241 

torpor,  241 

gouty  deposits,  241 

diabetes,  241 

-    dyspe))sia,  241 

glycosuria,  241 

skin  affections,  241 

liver  affections,  241 

resiiiratory  affec;tions,  241 

,  Hot,  240 

,  Muriated,  237-239 

,  Objects  of  using,  226-220 

,  Simple,  230-233 

,  Simple  alkaline,  233,  234 

,  Sulphur,  239,  240 

,  Tlierapeutic  uses  of,   220- 

229 

,  Uses  of,  226-229,  241 

Murexide  test,  3 

Muriated  mineral  waters,  237-239 


N 


Nauheim  waters,  238 
Necrotic  changes  and  gout,  11 
Nenndorf  waters,  240 
Nervous  disturbance  as  cause  of  gout, 
21-23 

influences  and  gout,  05,  96 

system  and  gout,  21-23 

Neuenahr  waters,  233,  241 
Neuralgia,  Gouty,  110 
Neuritis,  Gontv,  119,  120 

,  Treatment  of,  217 

Nitrogeuised  diet  and  uric  acid.  Go 
Nitrogenous  diets  and  gout,  140,  141 
Nuclein  formation  of  uric  acid,  72-77 


(Esophagismus,  Gouty,  116 
Orchitis,  Gouty,  125 


Parotitis,  Gouty,  125 
Paroxysm,  Cause  of  gouty,  101-103 
Pathologv  of  gout,  1-104 
Pfaefers  waters,  232,  241 
Pharyngitis,  Gouty,  116 
Plilebifis,  Gouty,  118,  119 

,  Treatment  of,  21t),  217 

Piperazine,  Effect  of,  180,  1S5,  186 
,  Experiments  with,  179,  180,  185, 

186 
Plumbism  and  gout,  50,  60,  m,  97 

and  uric  aci<l,  50 

Portal  congestion,  Treatnumt  of,  234 
Potassium  bicarbonate.  Experiments 

witli,  179-182,  187-180 
citrate,  Experiments  with,  179- 

183 
salts  and  gouty  deposits,  1S1-1S3, 

187-189 
Potato  ash,  Effect  of,  152 
Predisposing  causes  of  gout,  105-107 
Preventive  treatment  of  gout,  220,  221 


Prognosis  of  gout,  127 

Proteids  and  uric  acid,  05,  66 

Prurigo,  Gouty,  123 

Pruritus,  Gouty,  123 

Pseudo-am^ina  pectoris,  Treatment  of, 

216 
Psoriasis,  Goutv,  123 

,  Treatment  of,  218,  239 

Pulmonary  congestion,  Goutv,  118 
Purgatives  in  gout,  203,  204,  '233-239 


Q 

Quadriurate  and  vegetable  ashes,  169- 
172 

,  Decomposition  of,  178,  179 

Quadriurates,  Amorphous,  7 
,  Composition  of,  2 


R 


rs-81 


Ratio  of  uric  acid  to  urea, 

Reiclienhall  baths,  230 

Renal  affection  causing  gout.  62 

calculi,  Treatment  of,  218 

disease    and    uratic    deposition, 

54-57 

disease.  Treatment  of,  210,  211 

and  uric  acid  in  blood,  40, 

54-57 

formation  of  uric  acid,  37,  38 

origin  of  gout,  60-63 

Respiratory  affections  and  gout,  117, 
118 

— : ,  Mineral  waters  for,  241 

,  Treatment  of,  236,  2Jl 

Retrocedent  gout,  124,  125 

of  brain,  125 

of  lieart,  125 

of  intestines,  125 

—  — -  of  stomach,  125 

,  Treatment  of,  213,  214 

Rheinfelden  baths,  230 

Rheumatism  and  gout.  Distinction  of, 
126 

Rheumatoid  arthritis  and  gout,  Dis- 
tinction of,  126,  127 

Roberts's  standard  solvent,  87 

Royat  waters,  236,  241 


Saint-Honore  waters,  240 
Salicylates  contra-indicated  in  gout, 

107 

,  Treatment  of  gout  by,  103-197 

Salzbrunn  waters,  234 
Saturnine  gout,  113,  114 
Savoy  cabbage  ash.  Effect  of,  153 
Schinznacli  waters,  240 
Sciatica,  Gouty,  119 

,  Treatment  of,  217 

Seakale  ash,  Effect  of,  156 
Serpents,    Urinary  excrement  of,  S3, 

84 
Sex  and  gout,  105 
Simple  mineral  waters,  230-233 
Skin  affections  and  gout,  122,  123 
,  Mineral  waters  for,  241 


Index. 


247 


Skin  aflections,  Treatment  of,  218,  239 
Sodium    bicarbonate,      Exiierimeuts 

witli,  179-181,  184 

biurate,  2 

,  Causes  of  deposition  of,  92- 

100 

,  Formation  of,  3 

,  Solubility  of,  92 

,  Neutral  urate  of,  2,  17 

jihosphate,    Experiments    with, 

179,  180,  ISO 

quadriurate,  2 

Spas,  Miiienil  water,  231-240 
Spinacli,  Advantages  of,  173 
Spinadi  asli,  Etfect  of,  151 
Si>leen  and  uric  acid  formation,  40 
Strathpeffer  waters,  231,  240,  241 
Subacute  gout,  Treatment  of,  208,  209 
Sugar  aiid  gout,  14S 
Sulpliur  mineral  waters,  239,  240 

springs.  Cold,  24  J 

,  Hot,  240 

Suppressed  gout,  114 
Synthesis  of  uric  acid,  09,  70 


Tarasp-Sclmls  waters,  285,  241 

Teplitz  waters,  231,  241 

Test  for  uric  acid,  3 

Thymus  and  uric  acid  excretion,  74 

Toe,  Gouty  dejiosits  in  great,  101 

Tophaceous  gout.  111 

Tophi,  110,  111 

Toxic  agents  causing  gout,  59,  00 

Tracheins,  Gouty,  117 

Treatment  of  acute  gout,  201-205 

angina  pectoris,  215,  210 

clironic  gout,  208-212 

constipation,  203,  204,  233-239 

diabetes,  219,  220,  233 

dyspepsia,  233,  234,  230,  237 

gastro  -  intestinal  catarrh,    233, 

234,  237,  239,  241 

glycosuria,  219,  220,  233,  234 

gout,  199-241 

gout.  Preventive,  220,  221 

gouty  asthma,  230 

bronchitis,  236 

heart,  214 

ioints,    201,    202,     209-212, 

230-233 

neuritis,  217 

phlebitis,  210,  217 

sciatica.  217 

vertigo,  214 

hepatic  congestion,  233,  234,  237, 

239 

irregular  gout,  214-220 

irritable  temjier,  219 

metastatic  gout,  213,  214 

portal  congestion,  234 

pseudo-angina  pectoris,  216 

renal  calculi,  218 

retrucedent  gout,  213,  214 

skin  disorders,  218,  239 

subacute  gout,  20S,  209 

Turnij)  ash.  Effect  of,  155 
tops  ash,  Effect  of,  155 


Urates,  Neutral,  2,  17 

Uratic  deposit.  Formation  of,  86-89 

Uratic  deposits  and  renal  disease,  54- 

57 

.  Seats  of,  90 

Urea  a  normal  constituent  of  blood, 

44,  45 

and  uric  acid  ratio,  78-81 

,  Formation  of   uric  acid  from, 

08-72 
Uriage  waters,  240 
Uric  acid  absent  from  blood  in  health, 

43-47 

and  blood  disorders,  48 

lead  poisoning,  50 

nitrogenised  diet,  65 

nucleiu,  72-77 

proteids,  05,  60 

urea  ratio,  78-81 

calculi,  121 

,  Cause  of  abnormal  forma- 
tion of,  09 

,  Composition  of,  2 

compound  in  bluod,  2 

,  Daily  outpi.t  of,  201 

— ,  Deficient  excretion  of,  20-28 

■ — -,  Discovery  of,  4 

elimination   in   health,    SO, 

81 

excretion  and  diet,  05-07 

by  kidneys,  53 

in  gout,  'il,  28 

,  Formation  of,  34,  35,  68-77 

formed  from  urea,  68-72 

gravel,  121 

in  blood.  Detection  of,  31-34 

,  Estimation  of,  31-34 

of  anfemia,  48 

in  urine, Estimation  of,  29-31 

,  Introduction  into  blood  of, 

25,  82 
not  a  normal  constituent  of 

blood,  43-47 

not  a  poison,  9 

not  present  in  food,  77,  78 

■ ■ ,  Over-jtroduction  of,  20 

,  Promotion  of    elimination 

of,  209 

,  Renal  formation  of,  37,  38 

,  Salts  of,  2 

,  Sources  of,  34,  35 

,  Synthesis  of,  09,  70 

,  Test  for,  3 

,  Variations    in   elimination 

of,  81 
Urine,  Amorphous  urate  deposit  of, 

84-80 

,  Estimation  of  uric  acid  in,  29-31 

,  Examination  of,  200,  201 

of  chronic  gout,  112 

Urticaria,  Gouty,  123 


Vals  waters,  233,  241 

Vegetable  ashes.  Alkalinity  of,  158 

diet  and  uric  acid,  05,  00 

Vegetables  and  gout,  144,  150-175 


248 


Govt 


Vegetables,  Calcium  salts  in,  ]  62 

,  Chlorides  in,  165 

for  the  gouty,  173 

,  Phosphates  in,  103 

,  Potassium  salts  in,  160 

,  Sodium  salts  in,  161 

,  Sulphates  in,  104 

Vertigo  and  gout,  120 

,  Treatment  of  gouty,  214 

Vichv  -n-aters,  233,  241 
Vitte'l  waters,  233,  241 


W 

Waters,  Alkaline,  233,  234 

muriat-ed,  230,  237 

sulphated,  234-236 

,  Classification  of,  229,  230,  240, 

241 


Waters,  Cold  mineral,  240 

,  Hot  mineral,  240 

,  Muriated,  237-239 

,  Simple,  230-233 

,  Sulphur,  239,  240 

,  Uses  of  mineral,  220-229,  241 

Weilbach  uaters,  240 
Wiesbaden  waters,  237,  238,  241 
Wildbad  waters,  232,  241 
Wines,  Acidity  of,  140 

and  gout,  140-149 

,  Gout-inducing  powers   of,   146, 

148,  149 

suitable  in  gout,  225 

Woodhall  Spa  waters,  239 


Xanthin,  73 


Printed  Hy  Cassell  &  Companv,  Limited,  La  BtLLE  Sai'Vaob,  London,  E.G. 


